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  • 1
    ISSN: 1437-160X
    Keywords: Arthritis ; Monocytes ; Monoclonal antibody modulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Surface expression of 16 different membrane molecules was analyzed in peripheral blood and synovial fluid monocytes from patients with rheumatoid arthritis and reactive arthritis compared to controls. The most significant findings were modulated expression of function-associated FcRI, CR1, CR3, MHC class II and activation-associated CD31, M5, and M6 molecules in arthritis patients compared to controls. Of these molecules, only upregulated expression of MHC class II has previously been reported in synovial fluid monocytes of patients with rheumatoid arthritis.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0584
    Keywords: Granulocyte-macrophage colony-stimulating factor (GM-CSF) ; Granulocyte surface receptors ; Therapy monitoring
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In vitro activation of human granulocytes leads to altered expression of distinct surface antigens. Compared with the changes observed with classic activating reagents such as the phorbol ester PMA similar, but less pronounced alterations of surface antigen expression were observed upon granulocyte activation with human recombinant granulocyte-macrophage colony-stimulating factor (hrGM-CSF). In particular, stimulation with hrGM-CSF is followed by an enhanced expression of the complement receptors CD35 (CR1) and CD11b (CR3) while the low affinity Fc-γ receptor CD16 (FcRIII) is downregulated. In order to investigate whether there are similar effects under in vivo conditions, we studied the granulocytes from patients undergoing rhGM-CSF therapy before, during, and after treatment. We found a marked increase in CD35 (CR1) and CD11b (CR3) expression and a substantial decrease or even loss of CD16 (FcRIII) on these granulocytes. These changes correlated well with our in vitro data and occurred extremely rapidly after therapy onset. Furthermore, therapy monitoring using ratios calculated by the mean fluorescence channel numbers of CR and FcRIII stainings may combine the advantage of high sensitivity with high reproducibility as a result of the contrasting change in CR and FcRIII expression during granulocyte activation. Being nonparametric values, such ratios are not influenced by individual flow cytometry standardization. Taken together, these activation-associated changes of surface receptor expression and especially of CR over FcRIII ratios are useful parameters for monitoring the in vivo effects of rhGM-CSF.
    Type of Medium: Electronic Resource
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  • 3
    Publication Date: 2015-07-03
    Description: Dendritic cell (DC)–mediated inflammation induced via TLRs is promoted by MAPK-activated protein kinase (MK)-2, a substrate of p38 MAPK. In this study we show an opposing role of MK2, by which it consolidates immune regulatory functions in DCs through modulation of p38, ERK1/2-MAPK, and STAT3 signaling. During primary TLR/p38 signaling, MK2 mediates the inhibition of p38 activation and positively cross-regulates ERK1/2 activity, leading to a reduction of IL-12 and IL-1α/β secretion. Consequently, MK2 impairs secondary autocrine IL-1α signaling in DCs, which further decreases the IL-1α/p38 but increases the anti-inflammatory IL-10/STAT3 signaling route. Therefore, the blockade of MK2 activity enables human and murine DCs to strengthen proinflammatory effector mechanisms by promoting IL-1α–mediated Th1 effector functions in vitro. Furthermore, MK2-deficient DCs trigger Th1 differentiation and Ag-specific cytotoxicity in vivo. Finally, wild-type mice immunized with LPS in the presence of an MK2 inhibitor strongly accumulate Th1 cells in their lymph nodes. These observations correlate with a severe clinical course in DC-specific MK2 knockout mice compared with wild-type littermates upon induction of experimental autoimmune encephalitis. Our data suggest that MK2 exerts a profound anti-inflammatory effect that prevents DCs from prolonging excessive Th1 effector T cell functions and autoimmunity.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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