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  1. Article ; Online: CATH-2 and LL-37 increase mannose receptor expression, antigen presentation and the endocytic capacity of chicken mononuclear phagocytes.

    Kraaij, Marina D / van Dijk, Albert / Haagsman, Henk P

    Molecular immunology

    2017  Volume 90, Page(s) 118–125

    Abstract: ... chicken peripheral blood mononuclear cells (PBMCs). Treatment of chicken PBMCs with L-CATH-2, D-CATH-2 or ... LL-37 increased the percentage of mononuclear phagocytes, but decreased that of B cells. L-CATH-2, D ... increased antigen presentation capacity. Concomitantly, L-CATH-2, D-CATH-2 and LL-37 neutralized LPS-induced ...

    Abstract Cathelicidins display in vitro and in vivo immunomodulatory activities and are part of the innate immune system. Previously, we found that in ovo treatment with chicken cathelicidin CATH-2 partially protects young broilers against respiratory E. coli infection. To determine the cellular aspects of this protection, we investigated immunomodulatory effects of CATH-2 and the human cathelicidin LL-37 on primary chicken peripheral blood mononuclear cells (PBMCs). Treatment of chicken PBMCs with L-CATH-2, D-CATH-2 or LL-37 increased the percentage of mononuclear phagocytes, but decreased that of B cells. L-CATH-2, D-CATH-2 and LL-37 treatment of chicken PBMCs also enhanced the expression levels of mannose receptor MRC1 and antigen presentation markers MHCII, CD40 and CD86 on mononuclear phagocytes, indicating increased antigen presentation capacity. Concomitantly, L-CATH-2, D-CATH-2 and LL-37 neutralized LPS-induced cytokine production, while increasing the endocytic capacity. We conclude that L-CATH-2, D-CATH-2 and LL-37 can modulate the immune response of primary chicken immune cells by increasing mannose receptor expression, antigen presentation, endocytosis and neutralizing LPS-induced cytokine production and as a result augment activation of the adaptive immune system.
    MeSH term(s) Animals ; Antigen Presentation/immunology ; Antimicrobial Cationic Peptides/immunology ; B7-2 Antigen/metabolism ; CD40 Antigens/metabolism ; Cell Proliferation ; Cells, Cultured ; Chickens ; Cytokines/biosynthesis ; Endocytosis/immunology ; Humans ; Lectins, C-Type/biosynthesis ; Lectins, C-Type/immunology ; Mannose-Binding Lectins/biosynthesis ; Mannose-Binding Lectins/immunology ; Mononuclear Phagocyte System/immunology ; Receptors, Cell Surface/biosynthesis ; Receptors, Cell Surface/immunology
    Chemical Substances Antimicrobial Cationic Peptides ; B7-2 Antigen ; CD40 Antigens ; CMAP27 protein, chicken ; Cytokines ; Lectins, C-Type ; Mannose-Binding Lectins ; Receptors, Cell Surface ; mannose receptor ; ropocamptide (3DD771JO2H)
    Language English
    Publishing date 2017-07-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 424427-8
    ISSN 1872-9142 ; 0161-5890
    ISSN (online) 1872-9142
    ISSN 0161-5890
    DOI 10.1016/j.molimm.2017.07.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Immunomodulation and effects on microbiota after in ovo administration of chicken cathelicidin-2.

    Cuperus, Tryntsje / Kraaij, Marina D / Zomer, Aldert L / van Dijk, Albert / Haagsman, Henk P

    PloS one

    2018  Volume 13, Issue 6, Page(s) e0198188

    Abstract: ... has multiple immunomodulatory effects in vitro and the D-amino acid analog of this peptide has been ... for CATH-2 mediated in vivo protection have not been investigated so far. In this study, D-CATH-2 was ... variable, suggesting that it was strongly influenced by environmental factors. In both studies, in ovo D ...

    Abstract Host Defense Peptides (HDPs) such as cathelicidins are multifunctional effectors of the innate immune system with both antimicrobial and pleiotropic immunomodulatory functions. Chicken cathelicidin-2 (CATH-2) has multiple immunomodulatory effects in vitro and the D-amino acid analog of this peptide has been shown to partially protect young chicks from a bacterial infection. However, the mechanisms responsible for CATH-2 mediated in vivo protection have not been investigated so far. In this study, D-CATH-2 was administered in ovo and the immune status and microbiota of the chicks were investigated at 7 days posthatch to elucidate the in vivo mechanisms of the peptide. In three consecutive studies, no effects on numbers and functions of immune cells were found and only small changes were seen in gene expression of Peripheral Blood Mononuclear Cells (PBMCs). In two studies, intestinal microbiota composition was determined which was highly variable, suggesting that it was strongly influenced by environmental factors. In both studies, in ovo D-CATH-2 treatment caused significant reduction of Ruminococcaceae and Butyricicoccus in the cecum and Escherichia/Shigella in both ileum and cecum. In conclusion, this study shows that, in the absence of an infectious stimulus, in ovo administration of a CATH-2 analog alters the microbiota composition but does not affect the chicks' immune system posthatch.
    MeSH term(s) Animals ; Animals, Genetically Modified ; Antimicrobial Cationic Peptides/administration & dosage ; Antimicrobial Cationic Peptides/genetics ; Bone Marrow Cells/immunology ; Bone Marrow Cells/metabolism ; Cells, Cultured ; Chick Embryo ; Chickens/genetics ; Chickens/immunology ; Chickens/microbiology ; Immunity, Innate/genetics ; Immunomodulation/genetics ; Leukocytes, Mononuclear/immunology ; Leukocytes, Mononuclear/metabolism ; Microbiota/genetics ; Microbiota/immunology
    Chemical Substances Antimicrobial Cationic Peptides ; CMAP27 protein, chicken
    Language English
    Publishing date 2018-06-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0198188
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: CATH-2 and LL-37 increase mannose receptor expression, antigen presentation and the endocytic capacity of chicken mononuclear phagocytes

    Kraaij, Marina D / Albert van Dijk / Henk P. Haagsman

    Molecular Immunology. 2017,

    2017  

    Abstract: ... chicken peripheral blood mononuclear cells (PBMCs).Treatment of chicken PBMCs with L-CATH-2, D-CATH-2 or ... LL-37 increased the percentage of mononuclear phagocytes, but decreased that of B cells. L-CATH-2, D ... increased antigen presentation capacity. Concomitantly, L-CATH-2, D-CATH-2 and LL-37 neutralized LPS-induced ...

    Abstract Cathelicidins display in vitro and in vivo immunomodulatory activities and are part of the innate immune system. Previously, we found that in ovo treatment with chicken cathelicidin CATH-2 partially protects young broilers against respiratory E. coli infection. To determine the cellular aspects of this protection, we investigated immunomodulatory effects of CATH-2 and the human cathelicidin LL-37 on primary chicken peripheral blood mononuclear cells (PBMCs).Treatment of chicken PBMCs with L-CATH-2, D-CATH-2 or LL-37 increased the percentage of mononuclear phagocytes, but decreased that of B cells. L-CATH-2, D-CATH-2 and LL-37 treatment of chicken PBMCs also enhanced the expression levels of mannose receptor MRC1 and antigen presentation markers MHCII, CD40 and CD86 on mononuclear phagocytes, indicating increased antigen presentation capacity. Concomitantly, L-CATH-2, D-CATH-2 and LL-37 neutralized LPS-induced cytokine production, while increasing the endocytic capacity.We conclude that L-CATH-2, D-CATH-2 and LL-37 can modulate the immune response of primary chicken immune cells by increasing mannose receptor expression, antigen presentation, endocytosis and neutralizing LPS-induced cytokine production and as a result augment activation of the adaptive immune system.
    Keywords B-lymphocytes ; Escherichia coli ; antigen presentation ; cathelicidins ; chickens ; cytokines ; endocytosis ; humans ; immune response ; immunomodulators ; innate immunity ; mannose ; neutralization ; phagocytes
    Language English
    Size p. .
    Publishing place Elsevier Ltd
    Document type Article
    Note Pre-press version
    ZDB-ID 424427-8
    ISSN 1872-9142 ; 0161-5890
    ISSN (online) 1872-9142
    ISSN 0161-5890
    DOI 10.1016/j.molimm.2017.07.005
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: Chicken CATH-2 Increases Antigen Presentation Markers on Chicken Monocytes and Macrophages.

    Kraaij, Marina D / van Dijk, Albert / Scheenstra, Maaike R / van Harten, Roel M / Haagsman, Henk P / Veldhuizen, Edwin J A

    Protein and peptide letters

    2019  Volume 27, Issue 1, Page(s) 60–66

    Abstract: ... 2 and its all-D enantiomer D-CATH-2 increased MRC1 and MHC-II expression, markers ... for antigen presentation, on primary chicken monocytes, whereas LL-37 did not. D-CATH- 2 also increased the MRC1 and MHC-II ... by HD11 cells was inhibited by CATH-2 and D-CATH-2.: Conclusion: These results are a clear indication ...

    Abstract Background: Cathelicidins are a family of Host Defense Peptides (HDPs), that play an important role in the innate immune response. They exert both broad-spectrum antimicrobial activity against pathogens, and strong immunomodulatory functions that affect the response of innate and adaptive immune cells.
    Objective: The aim of this study was to investigate immunomodulation by the chicken cathelicidin CATH-2 and compare its activities to those of the human cathelicidin LL-37.
    Methods: Chicken macrophages and chicken monocytes were incubated with cathelicidins. Activation of immune cells was determined by measuring surface markers Mannose Receptor Ctype 1 (MRC1) and MHC-II. Cytokine production was measured by qPCR and nitric oxide production was determined using the Griess assay. Finally, the effect of cathelicidins on phagocytosis was measured using carboxylate-modified polystyrene latex beads.
    Results: CATH-2 and its all-D enantiomer D-CATH-2 increased MRC1 and MHC-II expression, markers for antigen presentation, on primary chicken monocytes, whereas LL-37 did not. D-CATH- 2 also increased the MRC1 and MHC-II expression if a chicken macrophage cell line (HD11 cells) was used. In addition, LPS-induced NO production by HD11 cells was inhibited by CATH-2 and D-CATH-2.
    Conclusion: These results are a clear indication that CATH-2 (and D-CATH-2) affect the activation state of monocytes and macrophages, which leads to optimization of the innate immune response and enhancement of the adaptive immune response.
    MeSH term(s) Amino Acid Sequence ; Animals ; Antigen Presentation/drug effects ; Antimicrobial Cationic Peptides/metabolism ; Biomarkers/metabolism ; Cathelicidins/metabolism ; Cell Line ; Chickens ; Cytokines/metabolism ; Gene Expression Regulation/drug effects ; Histocompatibility Antigens Class II/genetics ; Histocompatibility Antigens Class II/metabolism ; Humans ; Immunity, Innate/drug effects ; Immunomodulation/drug effects ; Lectins, C-Type/genetics ; Lectins, C-Type/metabolism ; Macrophages/metabolism ; Mannose-Binding Lectins/genetics ; Mannose-Binding Lectins/metabolism ; Monocytes/metabolism ; Receptors, Cell Surface/genetics ; Receptors, Cell Surface/metabolism
    Chemical Substances Antimicrobial Cationic Peptides ; Biomarkers ; Cathelicidins ; Cytokines ; Histocompatibility Antigens Class II ; Lectins, C-Type ; Mannose-Binding Lectins ; Receptors, Cell Surface ; mannose receptor ; ropocamptide (3DD771JO2H)
    Language English
    Publishing date 2019-07-30
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1280776-x
    ISSN 1875-5305 ; 0929-8665
    ISSN (online) 1875-5305
    ISSN 0929-8665
    DOI 10.2174/0929866526666190730125525
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Immunomodulation and effects on microbiota after in ovo administration of chicken cathelicidin-2.

    Tryntsje Cuperus / Marina D Kraaij / Aldert L Zomer / Albert van Dijk / Henk P Haagsman

    PLoS ONE, Vol 13, Iss 6, p e

    2018  Volume 0198188

    Abstract: ... has multiple immunomodulatory effects in vitro and the D-amino acid analog of this peptide has been ... for CATH-2 mediated in vivo protection have not been investigated so far. In this study, D-CATH-2 was ... variable, suggesting that it was strongly influenced by environmental factors. In both studies, in ovo D ...

    Abstract Host Defense Peptides (HDPs) such as cathelicidins are multifunctional effectors of the innate immune system with both antimicrobial and pleiotropic immunomodulatory functions. Chicken cathelicidin-2 (CATH-2) has multiple immunomodulatory effects in vitro and the D-amino acid analog of this peptide has been shown to partially protect young chicks from a bacterial infection. However, the mechanisms responsible for CATH-2 mediated in vivo protection have not been investigated so far. In this study, D-CATH-2 was administered in ovo and the immune status and microbiota of the chicks were investigated at 7 days posthatch to elucidate the in vivo mechanisms of the peptide. In three consecutive studies, no effects on numbers and functions of immune cells were found and only small changes were seen in gene expression of Peripheral Blood Mononuclear Cells (PBMCs). In two studies, intestinal microbiota composition was determined which was highly variable, suggesting that it was strongly influenced by environmental factors. In both studies, in ovo D-CATH-2 treatment caused significant reduction of Ruminococcaceae and Butyricicoccus in the cecum and Escherichia/Shigella in both ileum and cecum. In conclusion, this study shows that, in the absence of an infectious stimulus, in ovo administration of a CATH-2 analog alters the microbiota composition but does not affect the chicks' immune system posthatch.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2018-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article: The role of B cells in systemic sclerosis.

    Kraaij, Marina D / van Laar, Jacob M

    Biologics : targets & therapy

    2009  Volume 2, Issue 3, Page(s) 389–395

    Abstract: Systemic sclerosis (SSc) is a connective disease characterized by features of autoimmunity, vasculopathy, inflammation, and fibrosis. The disease typically starts with Raynaud's phenomenon, followed by skin thickening in the extremities due to ... ...

    Abstract Systemic sclerosis (SSc) is a connective disease characterized by features of autoimmunity, vasculopathy, inflammation, and fibrosis. The disease typically starts with Raynaud's phenomenon, followed by skin thickening in the extremities due to inflammation and fibrosis. Fibrosis results from excessive collagen production by fibroblasts, which constitutes the final common pathway of complex cellular interactions including B cells. Several studies have indicated that B cells may play a role in SSc. Lesional skin infiltrates from SSc patients consist of a variety of cells, including eosinophils, neutrophils, lymphocytes, plasma cells, and macrophages. Autoantibodies of several specificities are present in the serum of SSc patients of which antitopoisomerase 1 is the most common, and evidence has been gathered for a potential pathogenic role of some autoantibodies, eg, anti-PDGF antibodies. The blood of SSc patients contains an increased proportion of naïve B cells but a decreased proportion of memory B cells. Furthermore, serum levels of interleukin-6, an important pro-inflammatory cytokine, have been shown to correlate with skin fibrosis. Animal models of SSc have provided more in-depth information on the role of B lymphocytes, eg, through disruption of B cell function. In this review we will discuss the evidence that B cells are involved in the pathogenesis of SSc.
    Language English
    Publishing date 2009-04-29
    Publishing country New Zealand
    Document type Journal Article
    ZDB-ID 2415708-9
    ISSN 1177-5491 ; 1177-5475
    ISSN (online) 1177-5491
    ISSN 1177-5475
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The NOX2-mediated ROS producing capacity of recipient cells is associated with reduced T cell infiltrate in an experimental model of chronic renal allograft inflammation.

    Kraaij, Marina D / Koekkoek, Karin M / Gelderman, Kyra A / van Kooten, Cees

    Transplant immunology

    2014  Volume 30, Issue 2-3, Page(s) 65–70

    Abstract: We previously showed that anti-inflammatory Mph (Mph2) can both in vitro and in vivo induce regulatory T cells (Tregs) in a reactive oxygen species (ROS)-dependent fashion. As influx of Mph is an important characteristic of chronic inflammatory responses, ...

    Abstract We previously showed that anti-inflammatory Mph (Mph2) can both in vitro and in vivo induce regulatory T cells (Tregs) in a reactive oxygen species (ROS)-dependent fashion. As influx of Mph is an important characteristic of chronic inflammatory responses, we investigated the impact of NOX2-mediated ROS production by recipient cells in an experimental model of chronic allograft inflammation. We used a kidney transplantation (Tx) model with Lewis (Lew) rats as donor and congenic DA.Ncf1(DA/DA) (low ROS) and DA.Ncf1(E3/E3) (normal ROS) rats as recipients. At day 7 the contralateral kidney was removed, and the animals were sacrificed four weeks after Tx. Renal function and injury were monitored in serum and urine and the composition of the infiltrate was analyzed by immunohistochemistry. Four weeks after Tx, large leukocyte clusters were observed in the allograft, in which signs of ROS production could be demonstrated. These clusters showed no difference regarding composition of myeloid cells or the number of FoxP3 positive cells. However, T cell infiltrate was significantly reduced in the DA.Ncf1(E3/E3) recipients having normal ROS production. Therefore, this study suggests a regulatory effect of ROS on T cell infiltration, but no effect on other inflammatory cells in the allograft.
    MeSH term(s) Allografts ; Animals ; Disease Models, Animal ; Graft Rejection/genetics ; Graft Rejection/immunology ; Graft Rejection/pathology ; Inflammation/genetics ; Inflammation/immunology ; Inflammation/pathology ; Kidney Transplantation ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/immunology ; NADPH Oxidase 2 ; NADPH Oxidases/genetics ; NADPH Oxidases/immunology ; Rats ; Rats, Inbred Lew ; Reactive Oxygen Species/immunology ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/pathology
    Chemical Substances Membrane Glycoproteins ; Reactive Oxygen Species ; Cybb protein, rat (EC 1.6.3.-) ; NADPH Oxidase 2 (EC 1.6.3.-) ; NADPH Oxidases (EC 1.6.3.-)
    Language English
    Publishing date 2014-03
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1160846-8
    ISSN 1878-5492 ; 0966-3274
    ISSN (online) 1878-5492
    ISSN 0966-3274
    DOI 10.1016/j.trim.2013.12.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Prophylactic administration of chicken cathelicidin-2 boosts zebrafish embryonic innate immunity.

    Schneider, Viktoria A F / van Dijk, Albert / van der Sar, Astrid M / Kraaij, Marina D / Veldhuizen, Edwin J A / Haagsman, Henk P

    Developmental and comparative immunology

    2016  Volume 60, Page(s) 108–114

    Abstract: Chicken cathelicidin-2 (CATH-2) is a host defense peptide that exhibits immunomodulatory and antibacterial properties. Here we examined effects of CATH-2 in zebrafish embryos in the absence and presence of infection. Yolk-injection of 0.2-1.5 h post- ... ...

    Abstract Chicken cathelicidin-2 (CATH-2) is a host defense peptide that exhibits immunomodulatory and antibacterial properties. Here we examined effects of CATH-2 in zebrafish embryos in the absence and presence of infection. Yolk-injection of 0.2-1.5 h post-fertilized (hpf) zebrafish embryos with 2.6 ng/kg CATH-2 increased proliferation of phagocytic cells at 48 hpf by 30%. A lethal infection model was developed to test the prophylactic protective effect of CATH-2 peptide. Embryos (0.2-1.5 hpf) were injected with 2.6 ng/kg CATH-2, challenged with a lethal dose of fluorescently labeled Salmonella enteritidis pGMDs3 at 28 hpf and monitored for survival. Prophylactic treatment with CATH-2 was found to delay infection starting at 22 h post-infection (hpi). At 18-20 hpi, significantly lower (2-fold) fluorescence intensity and decreased bacterial loads were detected in peptide-treated embryos. Thus prophylactic administration of low CATH-2 concentrations confer partial protection in zebrafish embryos by boosting the innate immune system.
    MeSH term(s) Adjuvants, Immunologic/administration & dosage ; Animals ; Antimicrobial Cationic Peptides/administration & dosage ; Cell Proliferation ; Drug Evaluation, Preclinical ; Embryo, Nonmammalian/drug effects ; Embryo, Nonmammalian/immunology ; Fish Diseases/immunology ; Fish Diseases/microbiology ; Fish Diseases/prevention & control ; Immunity, Innate/drug effects ; Phagocytes/physiology ; Salmonella Infections, Animal/immunology ; Salmonella Infections, Animal/microbiology ; Salmonella Infections, Animal/prevention & control ; Salmonella enteritidis/immunology ; Zebrafish/immunology
    Chemical Substances Adjuvants, Immunologic ; Antimicrobial Cationic Peptides ; CMAP27 protein, chicken
    Language English
    Publishing date 2016-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 752411-0
    ISSN 1879-0089 ; 0145-305X
    ISSN (online) 1879-0089
    ISSN 0145-305X
    DOI 10.1016/j.dci.2016.02.023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: CD16+ Monocytes and Skewed Macrophage Polarization toward M2 Type Hallmark Heart Transplant Acute Cellular Rejection.

    van den Bosch, Thierry P P / Caliskan, Kadir / Kraaij, Marina D / Constantinescu, Alina A / Manintveld, Olivier C / Leenen, Pieter J M / von der Thüsen, Jan H / Clahsen-van Groningen, Marian C / Baan, Carla C / Rowshani, Ajda T

    Frontiers in immunology

    2017  Volume 8, Page(s) 346

    Abstract: Background: During acute heart transplant rejection, infiltration of lymphocytes and monocytes is followed by endothelial injury and eventually myocardial fibrosis. To date, no information is available on monocyte-macrophage-related cellular shifts and ... ...

    Abstract Background: During acute heart transplant rejection, infiltration of lymphocytes and monocytes is followed by endothelial injury and eventually myocardial fibrosis. To date, no information is available on monocyte-macrophage-related cellular shifts and their polarization status during rejection. Here, we aimed to define and correlate monocyte-macrophage endomyocardial tissue profiles obtained at rejection and time points prior to rejection, with corresponding serial blood samples in 25 heart transplant recipients experiencing acute cellular rejection. Additionally, 33 healthy individuals served as control.
    Materials and methods: Using histology, immunohistochemistry, confocal laser scan microscopy, and digital imaging expression of CD14, CD16, CD56, CD68, CD80, and CD163 were explored to define monocyte and macrophage tissue profiles during rejection. Fibrosis was investigated using Sirius Red stainings of rejection, non-rejection, and 1-year biopsies. Expression of co-stimulatory and migration-related molecules on circulating monocytes, and production potential for pro- and anti-inflammatory cytokines were studied using flow cytometry.
    Results: At tissue level, striking CD16+ monocyte infiltration was observed during rejection (
    Conclusion: CD16+ monocytes and M2 macrophages hallmark the correlates of heart transplant acute cellular rejection on tissue level and seem to be associated with fibrosis in the long term.
    Language English
    Publishing date 2017
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2017.00346
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: The role of B cells in systemic sclerosis

    Marina D Kraaij / Jacob M van Laar

    Biologics: Targets & Therapy, Vol 2008, Iss Issue 3, Pp 389-

    2008  Volume 395

    Abstract: Marina D Kraaij, Jacob M van LaarMusculoskeletal Research Group, Institute of Cellular Medicine ...

    Abstract Marina D Kraaij, Jacob M van LaarMusculoskeletal Research Group, Institute of Cellular Medicine, School of Clinical Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, United KingdomAbstract: Systemic sclerosis (SSc) is a connective disease characterized by features of autoimmunity, vasculopathy, inflammation, and fibrosis. The disease typically starts with Raynaud’s phenomenon, followed by skin thickening in the extremities due to inflammation and fibrosis. Fibrosis results from excessive collagen production by fibroblasts, which constitutes the final common pathway of complex cellular interactions including B cells. Several studies have indicated that B cells may play a role in SSc. Lesional skin infiltrates from SSc patients consist of a variety of cells, including eosinophils, neutrophils, lymphocytes, plasma cells, and macrophages. Autoantibodies of several specificities are present in the serum of SSc patients of which antitopoisomerase 1 is the most common, and evidence has been gathered for a potential pathogenic role of some autoantibodies, eg, anti-PDGF antibodies. The blood of SSc patients contains an increased proportion of naïve B cells but a decreased proportion of memory B cells. Furthermore, serum levels of interleukin-6, an important pro-inflammatory cytokine, have been shown to correlate with skin fibrosis. Animal models of SSc have provided more in-depth information on the role of B lymphocytes, eg, through disruption of B cell function. In this review we will discuss the evidence that B cells are involved in the pathogenesis of SSc.Keywords: B lymphocyte, systemic sclerosis, fibrosis
    Keywords Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2008-09-01T00:00:00Z
    Publisher Dove Medical Press
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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