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Title
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Human C-reactive protein activates monocyte-derived dendritic cells and induces dendritic cell-mediated T-cell activation
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Author
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Abstract
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| Objective-: Recent studies proposed a pathogenic role for C-reactive protein (CRP), an independent predictor of cardiovascular disease (CVD), in atherosclerosis. Therefore, we tested whether CRP may modulate dendritic cell (DC) function, because these professional antigen-presenting cells have been implicated in atherogenesis. Methods and Results-: Human monocyte-derived immature DCs were cultured with human CRP (0 to 60 [mu]g/mL) for 24 hours. Thereafter, activation markers were measured by flow-cytometry and DCs were cocultured with CFSE-labeled lymphocytes to measure T-cell proliferation and interferon (IFN)-[gamma] secretion after 8 days. Exposure to 60 [mu]g/mL CRP (n=5) induced an activated cell morphology and significant (CD40 increase MFI 5.23+/-0.28, P<0.01 paired t test; CD80 6.18+/-0.51, P<0.01) to modest (CD83 1.38+/-0.17, P<0.05, CCR7 1.60+/-0.29, P=0.05) upregulation of DC activation markers. The expression of CD86 and HLA-DR was high, but not affected. T-lymphocytes incubated with CRP-pulsed DCs displayed increased IFN-[gamma] secretion and proliferation (P<0.001). DC activation was concentration-dependent and detected from 2 [mu]g/mL CRP; the maximum effect was equivalent to that seen with 0.1 [mu]g/mL lipopolysaccharide (LPS). Polymyxin B abolished the LPS response, without influencing CRP effects. Finally, immunohistochemistry could demonstrate DC/CRP colocalization in human atherosclerotic lesions. Conclusions-: These findings suggest that CRP in plaques or found circulating in CVD patients can influence DC function during atherogenesis. |
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Language
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English
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Source (journal)
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Arteriosclerosis, thrombosis, and vascular biology / American Heart Association. - Dallas, Tex., 1995, currens
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Publication
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Dallas, Tex.
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2008
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ISSN
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1079-5642
1524-4636
[online]
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Volume/pages
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28
:3
(2008)
, p. 511-518
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ISI
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000253429000026
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Full text (Publisher's DOI)
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