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  • 1.
    Aleksejeva, Olga
    et al.
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Sokolov, A. V.
    Russia Saint-Petersburg State University, Russia.
    Marquez, I.
    University of Seville, Spain.
    Gustafsson, Anna
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Bushnev, S.
    Russian Academy of Sciences, Russia.
    Eriksson, Håkan
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Ljunggren, Lennart
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Shleev, Sergey
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV). Russian Academy of Sciences, Russia.
    Autotolerant ceruloplasmin based biocathodes for implanted biological power sources2021Inngår i: Bioelectrochemistry, ISSN 1567-5394, E-ISSN 1878-562X, Vol. 140Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    High-performance autotolerant bioelectrodes should be ideally suited to design implantable bioelectronic devices. Because of its high redox potential and ability to reduce oxygen directly to water, human ceruloplasmin, HCp, the only blue multicopper oxidase present in human plasma, appears to be the ultimate biocatalyst for oxygen biosensors and also biocathodes in biological power sources. In comparison to fungal and plant blue multicopper oxidases, e.g. Myrothecium verrucaria bilirubin oxidase and Rhus vernicifera laccase, respectively, the inflammatory response to HCp in human blood is significantly reduced. Partial purification of HCp allowed to preserve the native conformation of the enzyme and its biocatalytic activity. Therefore, electrochemical studies were carried out with the partially purified enzyme immobilised on nanostructured graphite electrodes at physiological pH and temperature. Amperometric investigations revealed low reductive current densities, i.e. about 1.65 µA cm−2 in oxygenated electrolyte and in the absence of any mediator, demonstrating nevertheless direct electron transfer based O2 bioelectroreduction by HCp for the first time. The reductive current density obtained in the mediated system was about 12 µA cm−2. Even though the inflammatory response of HCp is diminished in human blood, inadequate bioelectrocatalytic performance hinders its use as a cathodic bioelement in a biofuel cell.

    Fulltekst (pdf)
    fulltext
  • 2.
    Andersson, Linda
    et al.
    Malmö högskola, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Cirkic, Emina
    Malmö högskola, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Hellman, Peter
    Malmö högskola, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Eriksson, Håkan
    Malmö högskola, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Myeloid blood dendritic cells and monocyte-derived dendritic cells differ in their endocytosing capability2012Inngår i: Human Immunology, ISSN 0198-8859, E-ISSN 1879-1166, Vol. 73, nr 11, s. 1073-1081Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Human dendritic cells (DCs) constitute a heterogeneous population of antigen-presenting cells characterized by a unique capacity to stimulate naive T cells. The functions of DCs depend on the particular subset and in this study we compare two types of myeloid DCs: freshly isolated blood mDCs and in vitro generated monocyte-derived DCs (MoDCs), in their ability to accomplish endocytosis. In our hands, these two DC subtypes showed similarities in the expression of surface markers, but displayed clear differences in endocytic capacity. Freshly isolated blood mDCs showed a high propensity to capture and endocytose particles compared to in vitro generated MoDCs. The blood mDCs also showed a clear receptor-enhanced endocytosis when zeolite particles were co-adsorbed with IgG. On the other hand, the MoDCs differed remarkably compared to blood mDCs in the capture of ovalbumin and immune complexes. Interestingly, the MoDCs showed low endocytosis of IgG-coated particles but an efficient capture of immune complexes. The MoDCs also showed a high capacity to capture ovalbumin although with a relatively low degree of internalization. These data indicate distinct differences in the early process of endocytosis featured by mDCs and MoDCs, which is important to consider when choosing DC populations for future functional or clinical applications.

    Fulltekst (pdf)
    FULLTEXT01
  • 3. Andersson, Linda
    et al.
    Eriksson, Håkan
    Malmö högskola, Fakulteten för hälsa och samhälle (HS).
    De-aluminated zeolite Y as a Tool to Study Endocytosis, A Delivery System Revealing Differences between Human Peripheral Dendritic Cells2007Inngår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 66, nr 1, s. 52-61Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We report the use of nano-meter sized zeolite particles as a novel approach to follow the endosomal acidification and proteolysis inside a viable cell. The method was verified by using human peripheral monocytes, a well known endocytosing cell population. Zeolite particles were subsequently used to investigate the endocytosing mechanisms of human peripheral dendritic cells (DCs). Probes detecting pH neutral and acidic endosomes were adsorbed to de-aluminated zeolite Y, and used to detect endocytosis in immature human peripheral blood DCs. Both the myeloid (mDCs) and the plasmacytoid (pDCs) dendritic cell subsets had an endocytosing capacity comparable to peripheral blood monocytes. However, the majority of both subsets of DCs retained their endosomes at a neutral pH during the first hours after endocytosis and only a small number of the mDCs showed any formation of acidic endosomes. Proteolytic degradation of endocytosed proteins was detected using self-quenched DQ-ovalbumin adsorbed to zeolite particles. Interestingly, a clear difference in proteolytic degradation of endocytosed ovalbumin was observed between the two subsets of DCs. The mDC showed an efficient degradation of ovalbumin, while the pDC population displayed no or only minor proteolytic degradation. In conclusion, zeolite particles provide a useful tool to study the endocytosing mechanisms, and an efficient carrier of bio-molecules into the endosomal pathways of viable cells.

  • 4. Andersson, Linda
    et al.
    Eriksson, Håkan
    Malmö högskola, Fakulteten för hälsa och samhälle (HS).
    Detection of endocytosis using de-aluminated zeolite2006Konferansepaper (Annet vitenskapelig)
    Abstract [en]

    Nano-meter sized particles of de-aluminated zeolite Y has a high adsorption capacity of both low molecular weight bio-molecules and macromolecules. In this study we used de-aluminated zeolite Y as a novel approach to study the mechanisms of endocytosis in immature human peripheral blood dendritic cells (DCs). Probes detecting pH neutral and acidic endosomes were adsorbed to the zeolite and used as a tracer of the endosomal pathway of a cell in the form of acidification and lysosomal function. Both the myeloid (M-DCs) and the plasmacytoid (P-DCs) dendritic cell subsets showed an endocytosing capacity comparable to peripheral blood monocytes but only the M-DCs were able to form acidic endosomes after internalization of zeolite particles. Furthermore, during lipopolysaccharide (LPS) stimulation of the DCs population, an enhanced induction of acidic endosomes was only seen in the M-DC population. Proteolytic degradation of endocytosed proteins was detected using self-quenched DQ-ovalbumin adsorbed to zeolite particles and our results showed a clear difference between the two DC populations. The M-DC population, that showed formation of acidic endosomes, also showed proteolytic degradation of ovalbumin. The P-DC population on the other hand, showed no formation of acidic and no proteolytic degradation of ovalbumin. Various bio-molecules can be adsorbed by de-aluminated zeolites and in conclusion we propose the use of zeolite particles as a useful tool in the study of the endocytosing mechanisms of a cell.

  • 5. Andersson, Linda
    et al.
    Hellman, Peter
    Malmö högskola, Fakulteten för hälsa och samhälle (HS).
    Eriksson, Håkan
    Malmö högskola, Fakulteten för hälsa och samhälle (HS).
    Receptor-mediated endocytosis of particles by peripheral dendritic cells2008Inngår i: Human Immunology, ISSN 0198-8859, E-ISSN 1879-1166, nr 69, 625-633, 2008Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Human peripheral dendritic cells (DCs) are antigen-presenting cells with the ability to internalize antigen and present antigen-derived peptides to T cells. Human DCs express several receptors on the surface for endocytosis and other recognition receptors that bind to microbes or microbial products, which are internalized and processed. Here, we report the use of nanometer-size zeolite particles as a tool to study receptor-mediated endocytosis by the two subsets of immature DCs, myeloid (mDC) and plasmacytoid (pDC) dendritic cells. A major difference in receptor-mediated endocytosis was observed between the two populations of peripheral DCs. The pDC population demonstrated an almost complete lack of receptor-mediated endocytosis of zeolite particles, whereas the mDC population demonstrated a clear receptor-mediated endocytosis. Fc receptors are expressed by both peripheral DC populations and lipoteichoic acid (LTA) and lipopolysaccharide (LPS) are known ligands of the Toll-like receptor (TLR)-2 and TLR4, respectively, both TLRs expressed by human mDCs. An efficient receptormediated endocytosis of immunoglobulin G-, LTA-, and LPS-coated zeolite particles was observed by the mDC population and their endocytosing capacity depended strongly on the density of the ligand adsorbed onto the zeolite particles. In conclusion, an efficient receptor-mediated endocytosis was observed from the mDC population, whereas the pDCs demonstrated an almost complete lack of receptor-mediated endocytosis and nanometer-size dealuminated zeolite particles were a useful tool for studying receptor-mediated endocytosis in human peripheral DCs.

  • 6.
    Blum, Zoltan
    et al.
    Malmö högskola, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Eriksson, Håkan
    Malmö högskola, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Dealuminated Zeolites in Biological Systems2012Inngår i: Zeolites: Synthesis, Chemistry and Applications / [ed] Moisey K. Andreyev, Olya L. Zubkov, Nova Science Publishers, Inc., 2012, s. 295-302Kapittel i bok, del av antologi (Annet vitenskapelig)
    Abstract [en]

    Recent direct and indirect evidence have pointed to both biological reactivity and toxicity of micro- and nano-particles. Particle size appears to be a decisive factor and particles can enter cells in two ways; either through endocytosis, were particles enter the cell in an endosome; or by otherwise passing the cell membrane directly into the cytoplasm. Endocytosis covers sampling of small volumes of fluids and soluble molecules from the milieu surrounding the cell, as well as internalization of large particulate matter such as whole cells or cell fragments from the immediate vicinity of the cells. With respect to toxicity, it is important to identify the size and the chemical composition at which biological systems no longer regard the extraneous matter as particles and hence the material enters the cells directly, through other mechanisms than endocytosis.

  • 7.
    Dahm, Åsa
    et al.
    Malmö högskola, Teknik och samhälle (TS).
    Eriksson, Håkan
    Malmö högskola, Fakulteten för hälsa och samhälle (HS).
    Ultra-stable zeolites - a tool for in-cell chemistry2004Inngår i: Journal of Biotechnology, ISSN 0168-1656, E-ISSN 1873-4863, Vol. 111, nr 3, s. 279-290Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Ultrastable zeolite particles were used as vehicles to carry low molecular bio-active substances and macromolecules as proteins into viable cells. Zeolite particles that can be used for internalisation by phagocytosis were obtained from the non-sedimenting fraction of a commercially available zeolite preparation after 1 × g sedimentation. Protein adsorbed on the zeolite surface was shown to enter the endosomal pathway after phagocytosis and could be cleaved by the endosomal proteases. As a model of a low molecular weight bio-active molecule, the inhibitor of the cellular synthesis of nitrogen oxide, N-nitro-l-arginine methyl ester (L-NAME), was used. A partial inhibition of the cellular NO production was shown after utilizing zeolites as vehicles to introduce the inhibitor into the cells. A targeting of the intra-cellular enzymes that was at least 10 times more efficient was obtained by the use of zeolites as a carrier of the inhibitor, as opposed to addition of the inhibitor to the culture medium.

  • 8.
    Danielsson, Ravi
    et al.
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Eriksson, Håkan
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Aluminium adjuvants in vaccines: A way to modulate the immune response2021Inngår i: Seminars in Cell and Developmental Biology, ISSN 1084-9521, E-ISSN 1096-3634, Vol. 115, s. 3-9, artikkel-id S1084-9521(20)30202-0Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aluminium salts have been used as adjuvants in vaccines for almost a century, but still no clear understanding of the mechanisms behind the immune stimulating properties of aluminium based adjuvants is recognized. Aluminium adjuvants consist of aggregates and upon administration of a vaccine, the aggregates will be recognized and phagocytosed by sentinel cells such as macrophages or dendritic cells. The adjuvant aggregates will persist intracellularly, maintaining a saturated intracellular concentration of aluminium ions over an extended time. Macrophages and dendritic cells are pivotal cells of the innate immune system, linking the innate and adaptive immune systems, and become inflammatory and antigen-presenting upon activation, thus mediating the initiation of the adaptive immune system. Both types of cell are highly adaptable, and this review will discuss and highlight how the occurrence of intracellular aluminium ions over an extended time may induce the polarization of macrophages into inflammatory and antigen presenting M1 macrophages by affecting the: endosomal pH; formation of reactive oxygen species (ROS); stability of the phagosomal membrane; release of damage associated molecular patterns (DAMPs); and metabolism (metabolic re-programming). This review emphasizes that a persistent intracellular presence of aluminium ions over an extended time has the potential to affect the functionality of sentinel cells of the innate immune system, inducing polarization and activation. The immune stimulating properties of aluminium adjuvants is presumably mediated by several discrete events, however, a persistent intracellular presence of aluminium ions appears to be a key factor regarding the immune stimulating properties of aluminium based adjuvants.

  • 9.
    Danielsson, Ravi
    et al.
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Ferey, Nathan
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV). Univ Clermont Auvergne, Polytech Clermont Ferrand, F-63001 Clermont ferrand, France..
    Mile, Irene
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Eriksson, Håkan
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Metabolic Reprogramming of Macrophages upon In Vitro Incubation with Aluminum-Based Adjuvant2023Inngår i: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 24, nr 5, artikkel-id 4409Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aluminum-based adjuvants have been extensively used in vaccines. Despite their widespread use, the mechanism behind the immune stimulation properties of these adjuvants is not fully understood. Needless to say, extending the knowledge of the immune-stimulating properties of aluminum-based adjuvants is of utmost importance in the development of new, safer, and efficient vaccines. To further our knowledge of the mode of action of aluminum-based adjuvants, the prospect of metabolic reprogramming of macrophages upon phagocytosis of aluminum-based adjuvants was investigated. Macrophages were differentiated and polarized in vitro from human peripheral monocytes and incubated with the aluminum-based adjuvant Alhydrogel((R)). Polarization was verified by the expression of CD markers and cytokine production. In order to recognize adjuvant-derived reprogramming, macrophages were incubated with Alhydrogel((R)) or particles of polystyrene as control, and the cellular lactate content was analyzed using a bioluminescent assay. Quiescent M0 macrophages, as well as alternatively activated M2 macrophages, exhibited increased glycolytic metabolism upon exposure to aluminum-based adjuvants, indicating a metabolic reprogramming of the cells. Phagocytosis of aluminous adjuvants could result in an intracellular depot of aluminum ions, which may induce or support a metabolic reprogramming of the macrophages. The resulting increase in inflammatory macrophages could thus prove to be an important factor in the immune-stimulating properties of aluminum-based adjuvants.

    Fulltekst (pdf)
    fulltext
  • 10.
    Danielsson, Ravi
    et al.
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Sandberg, Tove
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Eriksson, Håkan
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Aluminium Adjuvants: a Nanomaterial used as Adjuvants in Human Vaccines for Decades2018Inngår i: Open Biotechnology Journal, ISSN 1874-0707, Vol. 12, s. 140-153Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Background: Aluminium salts have been used for decades in vaccines as adjuvants to facilitate the adaptive immune response against co-administered antigens. Two types of aluminium adjuvant are mostly used, aluminium oxyhydroxide and aluminium hydroxyphosphate. Both types of aluminium adjuvant consist of nanoparticles that form loose, micrometre sized aggregates at circumneutral pH. Aluminium adjuvants constitute a well-documented example of administration of nanomaterials to humanswith infrequent side effects and a safety record generally regarded as excellent. However, despite its prolonged use in human and veterinary medicine, the mechanisms behind the enhanced response and the immune stimulatory effect are still by and large unknown. Methods: The present paper reviews existing ideas regarding the immunostimulatory effects of aluminium adjuvants, with a focus on the induction of an inflammatory response by cellular stress. Reviewed information was obtained from peer-reviewed scientific papers published in 1988 to date with one exception, a paper published 1931. Results: Cellular stress causes extra cellular signalling of danger associated molecular patterns (DAMPs) and upon phagocytosis of aluminium adjuvants the cells need to manage the ingested particles. Conclusion: A persistent intracellular accumulation of aluminium adjuvants will be a solid depository of sparingly soluble aluminium salts maintaining a constant concentration of Al3+ ions in the cytoplasm and this will affect multiple biochemical processes. The cell will be under constant stress and DAMP signalling will occur and we would like to suggest the maintenance of a constant concentration Al3+ ions in the cytoplasm as a general underlying feature of the immune stimulation properties of aluminium adjuvants.

    Fulltekst (pdf)
    FULLTEXT01
  • 11.
    Danielsson, Ravi
    et al.
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Svensson, Andreas
    Falkman, Peter
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Eriksson, Håkan
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Tracing Aluminium-based Adjuvants: Their Interactions with Immune Competent Cells and their Effect on Mitochondrial Activity2018Inngår i: Open Immunology Journal, ISSN 1874-2262, Vol. 8, s. 1-15Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Studies revealing the immune stimulatory properties of aluminium-based adjuvants (ABAs) have been impaired by the absence of simple and reliable methods of tracing the adjuvants and their effect on biochemical processes upon endocytosis. Objective: To verify that labelling of ABAs with lumogallion doesn’t affect the physicochemical properties of the adjuvant; tracing cellular interaction with aluminium adjuvants; explore their effect on metabolic activity upon endocytosis. Methods: Physicochemical characterization by Z-potential and size distribution of ABAs labelled with lumogallion. Cellular interactions with ABAs by flow cytometry and confocal microscopy. Metabolic activity explored by measuring transformation of tetrazolium into formazan. Results: No or minor change of zeta potential and average particle size of lumogallion labelled aluminium oxyhydroxide, AlO(OH) and aluminium hydroxyphosphate, Al(OH)x(PO4 )y. Both phagocytosing and non-phagocytosing leukocytes became associated with ABAs at concentrations expected after in vivo administration of a vaccine. The ABAs were relatively toxic, affecting both lymphocytes and monocytes, and Al(OH)x(PO4 )y was more toxic than AlO(OH). Endocytosed aluminium adjuvant particles were not secreted from the cells and remained intracellular throughout several cell divisions. The presence of ABAs increased the mitochondrial activity of the monocytic cell line THP-1 and peripheral monocytes, as based on the transformation of tetrazolium into formazan. Conclusion: Lumogallion labelled ABAs is a valuable tool tracing interactions between ABAs and cells. Labelled ABAs can be traced intracellularly and ABAs are likely to remain intracellular for a long period of time. Intracellular ABAs increase the mitochondrial activity and the presence of intracellular Al ions is suggested to cause an increased mitochondrial activity. Keywords: Aluminium based adjuvant, Lumogallion, Mitochondrial activity, MTT assay, Phagocytosis, ABAS, Zeolites.

    Fulltekst (pdf)
    FULLTEXT01
  • 12.
    Eriksson, Håkan
    Malmö högskola, Fakulteten för hälsa och samhälle (HS).
    Controlled release of preservatives using dealuminated zeolite Y2008Inngår i: Journal of Biochemical and Biophysical Methods, ISSN 0165-022X, E-ISSN 1872-857X, Vol. 70, nr 6, s. 1139-1144Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study demonstrates that dealuminated zeolite Y can act as a depot after adsorption of phenol derived preservatives. Upon suspension of zeolite loaded with the preservative m-cresol, equilibrium was quickly reached between free and adsorbed m-cresol. The equilibrium concentration of m-cresol was below 1 mM, however, it was enough to kill bacteria such as Escherichia coli and Staphylococcus aureus under metabolically active conditions. Killing of bacteria were not obtained under non-proliferating conditions and m-cresol was only released from the zeolite upon bacterial activity. Together, these results demonstrate an interesting potential use of dealuminated zeolite Y containing adsorbed preservatives for preventing microbial growth in numerous applications in industry and clinical setting.

  • 13. Exley, Christopher
    et al.
    Siesjö, Peter
    Eriksson, Håkan
    Malmö högskola, Fakulteten för hälsa och samhälle (HS).
    The immunobiology of aluminium adjuvants: how do they really work?2010Inngår i: Trends in immunology, ISSN 1471-4906, E-ISSN 1471-4981, Vol. 31, nr 3, s. 103-109Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aluminium adjuvants potentiate the immune response, thereby ensuring the potency and efficacy of typically sparingly available antigen. Their concomitant critical importance in mass vaccination programmes may have prompted recent intense interest in understanding how they work and their safety. Progress in these areas is stymied, however, by a lack of accessible knowledge pertaining to the bioinorganic chemistry of aluminium adjuvants, and, consequently, the inappropriate application and interpretation of experimental models of their mode of action. The objective herein is, therefore, to identify the many ways that aluminium chemistry contributes to the wide and versatile armoury of its adjuvants, such that future research might be guided towards a fuller understanding of their role in human vaccinations.

  • 14.
    Hellman, Peter
    et al.
    Malmö högskola, Fakulteten för hälsa och samhälle (HS).
    Andersson, Linda
    Eriksson, Håkan
    Malmö högskola, Fakulteten för hälsa och samhälle (HS).
    Ligand surface density is important for efficient capture of immunoglobulin and phosphatidylcholine coated particles by human peripheral dendritic cells2009Inngår i: Cellular Immunology, ISSN 0008-8749, E-ISSN 1090-2163, Vol. 258, nr 2, s. 123-130Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A unique property of dealuminated zeolite particles is the exceptional ability to bind both hydrophilic and hydrophobic biomolecules without any covalent linkages. By adsorbing phospholipids onto the particle surface, capture of particles by human peripheral myeloid dendritic cells (mDCs) was observed. Capture of zeolite particles was only seen when a low density of phosphatidylcholine was present on the particles, indicating a specific recognition of the structural features realised by phosphatidylcholine after adsorption on the particle. Adsorbing IgG on the particles revealed capture by mDCs that was dependent upon the density of the IgG molecules. To obtain a smaller particle exposing a high density of IgG molecules, immune complexes (ICs) were formed and both mDCs and pDCs (peripheral plasmacytoid DCs) captured immune complexes, although the mDCs showed a more efficient capture of ICs. As expected, mDCs captured and internalized ICs, whereas pDCs captured ICs but showed no internalization of ICs.

  • 15.
    Hellman, Peter
    et al.
    Malmö högskola, Fakulteten för hälsa och samhälle (HS).
    Eriksson, Håkan
    Malmö högskola, Fakulteten för hälsa och samhälle (HS).
    EARLY ACTIVATION MARKERS EXPRESSED BY HUMAN PERIPHERAL DENDRITIC CELLS2006Konferansepaper (Annet vitenskapelig)
    Abstract [en]

    EARLY ACTIVATION MARKERS EXPRESSED BY HUMAN PERIPHERAL DENDRITIC CELLS Peter Hellman and Håkan Eriksson University of Malmoe, Department of Biomedical Laboratory Science E-mail address: peter.hellman@hs.mah.se Two major populations of immature dendritic cells, myeloid (M-DCs) and plasmacytoid (P-DCs) can be identified in human peripheral blood. Activation of these subsets through their Toll-like receptors (TLRs) (TLR4 for M-DCs and TLR9 for P-DCs) induced production of the chemokine Il-8, already within two hours of stimulation. The production of IL-8 preceded the expression of the activation marker CD40 in both M-DCs and P-DCs. Although both populations of DCs secreted Il-8 upon activation, the levels of Il-8 produced was several times higher in the M-DCs compared to the P-DCs population. Before activation both subsets of DCs expressed the IL-8 receptor type B (CD128b), however, upon stimulation the Il-8 receptor became undetectable in both M-DCs and P-DCs. Increased expression of MHC class II molecules is regarded as an early activation marker of DCs. However, only the P-DCs showed a significantly increased expression of MHC class II after 4 hours of stimulation through TLR9. Noteworthy, the M-DCs showed an unexpected increase of MHC class II molecules after conditioning in medium for 4 hours, and no further increase in MHC class II expression after stimulation through TLR4 was observed. In conclusion, we propose that during activation of human DCs the production of Il-8 and loss of CD128b are the earliest signs of activation preceding both MHC class II, CD40, CD80 and CD86 expression.

  • 16.
    Hellman, Peter
    et al.
    Malmö högskola, Fakulteten för hälsa och samhälle (HS).
    Eriksson, Håkan
    Malmö högskola, Fakulteten för hälsa och samhälle (HS).
    Early Activation Markers of Human Peripheral Dendritic Cells2007Inngår i: Human Immunology, ISSN 0198-8859, E-ISSN 1879-1166, Vol. 68, nr 5, s. 324-333Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Two major populations of dendritic cells (DCs), myeloid and plasmacytoid, can be isolated from human peripheral blood, and are distinguished by differential expression of the cell surface markers CD11c and CD123. These two populations of DCs also are different in their expression Toll-like receptor (TLR’s), receptors involved in their activation. To investigate the early events during activation of peripheral DCs, the cells were stimulated in vitro with ligands for TLR-4 (as in lipopolysaccharides) (LPS) or TLR-9 (CpG-containing oligonucleotide) (CpG). The earliest change in protein expression detected after stimulating peripheral DCs with LPS or CpG was increased production of the chemokine (IL)-8. Enhanced production of IL-8 occurred already within 2 hours of stimulation in both myeloid dendritic cells (M-DCs) and plasmacytoid dendritic cells (P-DCs), and preceded expression of the well established activation marker CD40. Although both populations of DCs secreted IL-8 upon activation, the levels of IL-8 produced was several times higher within the M-DCs compared to the P-DCs population. Before activation, both subsets of DCs expressed the IL-8 receptor type B (CD128b), but after stimulation the IL-8 receptor was down-regulated in both populations of DCs. Increased expression of MHC class II molecules is generally regarded as an early activation marker of DCs. However, only the P-DCs showed a significant up-regulation of MHC class II after stimulation. The M-DC population up-regulated MHC class II without any prior activation, thus care should be taken using increased expression of MHC class II molecules as an early activation marker of peripheral M-DCs after activation in vitro. In conclusion, we propose that during activation of human DCs the production of IL-8 and loss of CD128b are the earliest signs of activation preceding both MHC class II, CD40, CD80 and CD86 expression.

    Fulltekst (pdf)
    FULLTEXT01
  • 17.
    Johnsdotter, Sara
    et al.
    Malmö högskola, Fakulteten för hälsa och samhälle (HS), Institutionen för socialt arbete (SA).
    Eriksson, Håkan
    Malmö högskola, Fakulteten för hälsa och samhälle (HS), Institutionen för socialt arbete (SA).
    Commentary: Integrating social aspects into biomedicine2013Inngår i: Journal of Modern Medicinal Chemistry, ISSN 2308-8044, Vol. 1, nr 1, s. 61-63Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Modern biomedicine excels in discoveries in areas such as identification of pathogens and biochemical pathways, and the unveiling of genetic information. This remarkable development had its starting point back in the 19th century with the discovery of how microorganisms were related to disease. Until this point in time physicians primarily had had to rely on patients’ subjective illness experiences and social behavior in deciding diagnosis and treatment. When illness and disease moved into the laboratories the role of social and cultural factors for bodily processes was almost totally discarded. During the last decades it has become increasingly clear that an all-encompassing understanding of physiology and pathology requires that social and cultural factors be taken into consideration. The high placebo effect obtained during clinical trials is evidence of this. The pathways of the placebo effect are slowly being uncovered and this research testifies to the importance of factors not traditionally pertaining to biochemistry. Among the studies investigating into the interface between biochemical activity and social life, there are those showing associations between emotions and production of cytokines in inflammatory reactions, and how psychosocial stress might induce both depression and inflammation through activation of the nervous system. Consequently, future research needs to be multidisciplinary in order to reveal and identify areas of biomedicine so far missed. Collaboration between biomedical researchers and scholars from the social sciences and the humanities has a potential to capture more complex relations in the field of health and disease, and, in the end, make scientific contributions that better mirror the intricate conditions of human life.

    Fulltekst (pdf)
    FULLTEXT01
  • 18. Ketelsen, Anna
    et al.
    Eriksson, Håkan
    Malmö högskola, Fakulteten för hälsa och samhälle (HS).
    SENSITIVE DETECTION OF HYDROPHOBIC ANTIGENS USING A NOVEL LIPID-AGGREGATE BASED ELISA2008Inngår i: JIM - Journal of Immunological Methods, ISSN 0022-1759, E-ISSN 1872-7905, nr 2008Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Antibodies against hydrophobic antigens are common in several autoimmune diseases. However, detection of such antibodies by standard immune-assays, such as ELISA, is problematic, in part because of the problems with coating hydrophobic molecules onto polystyrene multi-well plates. We describe a novel method of stably associating hydrophobic antigens to ELISA plates. By mixing the antigen with a hydrophobic molecule containing a hydrophilic anchor, we generate mixed lipid aggregates that can attach to ELISA plates, and are resistant to detergent wash. Using the ganglioside GM-1 and phosphatidylethanolamine conjugated to the hapten DNP (dinitrophenyl) as model antigens, we show that hydrophobic antigens incorporated into mixed lipid aggregates expose their antigenic determinants in a correct configuration. The detection limit of both GM-1 and DNP-PE was considerably improved compared to when these antigens were coated on ELISA plates using organic solvents. Furthermore GM-1 incorporated into mixed lipid aggregates can be detected by specific antibodies in patient serum. The method of incorporating hydrophobic antigens into mixed lipid aggregates for stable association to ELISA plates can presumably be applied to a vast array of hydrophobic antigens, and may well be developed into a large scale screening system for serum reactivity towards different hydrophobic antigens.

  • 19.
    Kopecky, Jan
    et al.
    Lund Univ, Fac Med, Dept Clin Sci Lund, Glioma Immunotherapy Grp,Div Neurosurg, Barngatan 4, S-22185 Lund, Sweden..
    Perez, Julio Enriquez
    Lund Univ, Fac Med, Dept Clin Sci Lund, Glioma Immunotherapy Grp,Div Neurosurg, Barngatan 4, S-22185 Lund, Sweden..
    Eriksson, Håkan
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Visse, Edward
    Lund Univ, Fac Med, Dept Clin Sci Lund, Glioma Immunotherapy Grp,Div Neurosurg, Barngatan 4, S-22185 Lund, Sweden..
    Siesjo, Peter
    Lund Univ, Fac Med, Dept Clin Sci Lund, Glioma Immunotherapy Grp,Div Neurosurg, Barngatan 4, S-22185 Lund, Sweden.;Skane Univ Hosp, Dept Clin Sci Lund, Sect Neurosurg, Lund, Sweden..
    Darabi, Anna
    Lund Univ, Fac Med, Dept Clin Sci Lund, Glioma Immunotherapy Grp,Div Neurosurg, Barngatan 4, S-22185 Lund, Sweden..
    Intratumoral administration of the antisecretory peptide AF16 cures murine gliomas and modulates macrophage functions2022Inngår i: Scientific Reports, E-ISSN 2045-2322, Vol. 12, nr 1, artikkel-id 4609Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Glioblastoma has remained the deadliest primary brain tumor while its current therapy offers only modest survival prolongation. Immunotherapy has failed to record notable benefits in routine glioblastoma treatment. Conventionally, immunotherapy relies on T cells as tumor-killing agents; however, T cells are outnumbered by macrophages in glioblastoma microenvironment. In this study, we explore the effect of AF16, a peptide from the endogenous antisecretory factor protein, on the survival of glioma-bearing mice, the tumor size, and characteristics of the tumor microenvironment with specific focus on macrophages. We elucidate the effect of AF16 on the inflammation-related secretome of human and murine macrophages, as well as human glioblastoma cells. In our results, AF16 alone and in combination with temozolomide leads to cure in immunocompetent mice with orthotopic GL261 gliomas, as well as prolonged survival in immunocompromised mice. We recorded decreased tumor size and changes in infiltration of macrophages and T cells in the murine glioma microenvironment. Human and murine macrophages increased expression of proinflammatory markers in response to AF16 treatment and the same effect was seen in human primary glioblastoma cells. In summary, we present AF16 as an immunomodulatory factor stimulating pro-inflammatory macrophages with a potential to be implemented in glioblastoma treatment protocols.

    Fulltekst (pdf)
    fulltext
  • 20.
    Mile, Irene
    et al.
    Malmö högskola, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Svensson, Andreas
    Darabi, Anna
    Mold, Matthew
    Siesjö, Peter
    Eriksson, Håkan
    Malmö högskola, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Al adjuvants can be tracked in viable cells by lumogallion staining2015Inngår i: JIM - Journal of Immunological Methods, ISSN 0022-1759, E-ISSN 1872-7905, Vol. 422, s. 87-94Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The mechanism behind the adjuvant effect of aluminum salts is poorly understood notwithstanding that aluminum salts have been used for decades in clinical vaccines. In an aqueous environment and at a nearly neutral pH, the aluminumsalts form particulate aggregates, and one plausible explanation of the lack of information regarding the mechanisms could be the absence of an efficientmethod of tracking phagocytosed aluminum adjuvants and thereby the intracellular location of the adjuvant. In this paper, we want to report upon the use of lumogallion staining enabling the detection of phagocytosed aluminum adjuvants inside viable cells. Including micromolar concentrations of lumogallion in the culture medium resulted in a strong fluorescence signal from cells that had phagocytosed the aluminum adjuvant. The fluorescence appeared as spots in the cytoplasm and by confocal microscopy and co-staining with probes presenting fluorescence in the far-red region of the spectrum, aluminum adjuvants could to a certain extent be identified as localized in acidic vesicles, i.e., lysosomes. Staining and detection of intracellular aluminum adjuvants was achieved not only by diffusion of lumogallion into the cytoplasm, thereby highlighting the presence of the adjuvant, but also by pre-staining the aluminum adjuvant prior to incubation with cells. Pre-staining of aluminum adjuvants resulted in bright fluorescent particulate aggregates that remained fluorescent for weeks and with only a minor reduction of fluorescence upon extensive washing or incubation with cells. Both aluminum oxyhydroxide and aluminum hydroxyphosphate, two of the most commonly used aluminum adjuvants in clinical vaccines, could be pre-stained with lumogallion and were easily tracked intracellularly after incubation with phagocytosing cells. Staining of viable cells using lumogallion will be a useful method in investigations of the mechanisms behind aluminum adjuvants' differentiation of antigen-presenting cells into inflammatory cells. Information will be gained regarding the phagosomal pathways and the events inside the phagosomes, and thereby the ultimate fate of phagocytosed aluminum adjuvants could be resolved.

  • 21. Mold, Matt
    et al.
    Eriksson, Håkan
    Malmö högskola, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Siesjö, Peter
    Darabi, Anna
    Shardlow, Emma
    Exley, Christopher
    Unequivocal identification of intracellular aluminium adjuvant in a monocytic THP-1 cell line2014Inngår i: Scientific Reports, E-ISSN 2045-2322, nr 4, artikkel-id 6287Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aluminium-based adjuvants (ABA) are the predominant adjuvants used in human vaccinations. While a consensus is yet to be reached on the aetiology of the biological activities of ABA several studies have identified shape, crystallinity and size as critical factors affecting their adjuvanticity. In spite of recent advances, the fate of ABA following their administration remains unclear. Few if any studies have demonstrated the unequivocal presence of intracellular ABA. Herein we demonstrate for the first time the unequivocal identification of ABA within a monocytic (THP-1) cell line, using lumogallion as a fluorescent molecular probe for aluminium. Use of these new methods revealed that particulate ABA was only found in the cell cytoplasm. Transmission electron microscopy revealed that ABA were contained within vesicle-like structures of approximately 0.5–1 μm in diameter.

    Fulltekst (pdf)
    FULLTEXT01
  • 22.
    Ohlsson, Lars
    et al.
    Malmö högskola, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Exley, Christopher
    Darabi, Anna
    Sandén, Emma
    Siesjö, Peter
    Eriksson, Håkan
    Malmö högskola, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Aluminium based adjuvants and their effects on mitochondria and lysosomes of phagocytosing cells2013Inngår i: Journal of Inorganic Biochemistry, ISSN 0162-0134, E-ISSN 1873-3344, Vol. 128, s. 229-236Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aluminium oxyhydroxide, Al(OH)3 is one of few compounds approved as an adjuvant in human vaccines. However, the mechanism behind its immune stimulating properties is still poorly understood. In vitro co- culture of an aluminium adjuvant and the human monocytic cell line THP-1 resulted in reduced cell proliferation. Inhibition occurred at concentrations of adjuvant several times lower than would be found at the injection site using a vaccine formulation containing an aluminium adjuvant. Based on evaluation of the mitochondrial membrane potential, THP-1 cells showed no mitochondrial rupture after co-culture with the aluminium adju- vant, instead an increase in mitochondrial activity was seen. The THP-1 cells are phagocytosing cells and after co-culture with the aluminium adjuvant the phagosomal pathway was obstructed. Primary or early phagosomes mature into phagolysosomes with an internal pH of 4.5 – 5 and carry a wide variety of hydrolysing enzymes. Co-culture with the aluminium adjuvant yielded a reduced level of acidic vesicles and cathepsin L activity, a proteolytic enzyme of the phagolysosomes, was almost completely inhibited. THP-1 cells are an appropriate in vitro model in order to investigate the mechanism behind the induction of a phagocytosing antigen presenting cell into an inflammatory cell by aluminium adjuvants. Much information will be gained by investigating the phagosomal pathway and what occurs inside the phagosomes and to elucidate the ultimate fate of phagocytosed aluminium particles.

  • 23.
    Sternbæk, Louise
    et al.
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV). Malmö universitet, Biofilms Research Center for Biointerfaces. Phase Holographic Imaging AB, SE-223 63 Lund, Sweden.
    Kimani, Martha
    Chemical and Optical Sensing Division, Bundesanstalt für Materialforschung und-prüfung (BAM), DE-12489 Berlin, Germany.
    Gawlitza, Kornelia
    Chemical and Optical Sensing Division, Bundesanstalt für Materialforschung und-prüfung (BAM), DE-12489 Berlin, Germany.
    Rurack, Knut
    Chemical and Optical Sensing Division, Bundesanstalt für Materialforschung und-prüfung (BAM), DE-12489 Berlin, Germany.
    Janicke, Birgit
    Phase Holographic Imaging AB, SE-223 63 Lund, Sweden.
    Alm, Kersti
    Phase Holographic Imaging AB, SE-223 63 Lund, Sweden.
    Gjörloff Wingren, Anette
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV). Malmö universitet, Biofilms Research Center for Biointerfaces.
    Eriksson, Håkan
    Malmö universitet, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Molecularly Imprinted Polymers Exhibit Low Cytotoxic and Inflammatory Properties in Macrophages In Vitro2022Inngår i: Applied Sciences, E-ISSN 2076-3417, Vol. 12, s. 1-16, artikkel-id 6091Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Molecularly imprinted polymers (MIPs) against sialic acid (SA) have been developed as a detection tool to target cancer cells. Before proceeding to in vivo studies, a better knowledge of the overall effects of MIPs on the innate immune system is needed. The aim of this study thus was to exemplarily assess whether SA-MIPs lead to inflammatory and/or cytotoxic responses when administered to phagocytosing cells in the innate immune system. The response of monocytic/macrophage cell lines to two different reference particles, Alhydrogel and PLGA, was compared to their response to SA-MIPs. In vitro culture showed a cellular association of SA-MIPs and Alhydrogel, as analyzed by flow cytometry. The reference particle Alhydrogel induced secretion of IL-1β from the monocytic cell line THP-1, whereas almost no secretion was provoked for SA-MIPs. A reduced number of both THP-1 and RAW 264.7 cells were observed after incubation with SA-MIPs and this was not caused by cytotoxicity. Digital holographic cytometry showed that SA-MIP treatment affected cell division, with much fewer cells dividing. Thus, the reduced number of cells after SA-MIP treatment was not linked to SA-MIPs cytotoxicity. In conclusion, SA-MIPs have a low degree of inflammatory properties, are not cytotoxic, and can be applicable for future in vivo studies.

    Fulltekst (pdf)
    fulltext
  • 24. Svensson, Andreas
    et al.
    Eriksson, Håkan
    Malmö högskola, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Tracing aluminium adjuvants in viable cells2016Inngår i: Atlas of Science, nr February 29Artikkel i tidsskrift (Annet vitenskapelig)
    Fulltekst (pdf)
    FULLTEXT01
  • 25. Svensson, Andreas
    et al.
    Sandberg, Tove
    Malmö högskola, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Siesjö, Peter
    Eriksson, Håkan
    Malmö högskola, Fakulteten för hälsa och samhälle (HS), Institutionen för biomedicinsk vetenskap (BMV).
    Sequestering of damage-associated molecular-patterns (DAMPs): a possible mechanism affecting the immune stimulating properties of aluminium adjuvants2017Inngår i: Immunologic research, ISSN 0257-277X, E-ISSN 1559-0755, Vol. 65, nr 6, s. 1164-1175Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aluminium based adjuvants (ABAs) have been used in human and veterinary vaccines for decades and for a long time the adjuvant properties were believed to be mediated by an antigen depot at the injection site, prolonging antigen exposure to the immune system. The depot hypothesis is today more or less abandoned, and instead replaced by the assumption that ABAs induce an inflammation at the injection site. Induction of an inflammatory response is consistent with immune activation initiated by recognition of molecular patterns associated with danger or damage (DAMPs), and the latter are derived from endogenous molecules that normally reside intracellularly. When extracellularly expressed, because of damage, stress or cell death, a sterile inflammation is induced. In this paper, we report the induction of DAMP release by viable cells after phagocytosis of aluminium based adjuvants. Two of the most commonly used ABAs in pharmaceutical vaccine formulations, aluminium oxyhydroxide and aluminium hydroxyphosphate, induced a vigorous extracellular expression of the two DAMP molecules calreticulin and HMGB1. Concomitantly, extracellular adjuvant particles adsorbed the DAMP molecules released by the cells whereas IL-1, a previously reported inflammatory mediator induced by ABAs, was not absorbed by the adjuvants. Induction of extracellular expression of the two DAMP molecules was more prominent using aluminium hydroxyphosphate compared to aluminium oxyhydroxide, whereas the extracellular adsorption of the DAMP molecules was more pronounced with the latter. Furthermore, is hypothesised how induction of DAMP expression by ABAs and their concomitant adsorption by extra cellular adjuvants may affect the inflammatory properties of ABAs.

    Fulltekst (pdf)
    FULLTEXT01
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