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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:511.)
© 2008 American Heart Association, Inc.

Cell Biology/Signaling

Human C-Reactive Protein Activates Monocyte-Derived Dendritic Cells and Induces Dendritic Cell-Mediated T-Cell Activation

Emily A. Van Vré; Hidde Bult; Vicky Y. Hoymans; Viggo F.I. Van Tendeloo; Christiaan J. Vrints; Johan M. Bosmans

From the Departments of Cardiology (E.A.V.V., C.J.V., J.B.) and Pharmacology (H.B.), University of Antwerp, Wilrijk, Belgium and the Centre for Regenerative Medicine and Cell Therapy, Departments of Cardiology (V.Y.H., C.J.V., J.B.) and Experimental Haematology (V.F.I.V.T.), University Hospital of Antwerp, Edegem, Belgium.

Correspondence to Emily A. Van Vré, Division of Cardiology, University of Antwerp, B-2610 Wilrijk, Belgium. E-mail emily.vanvre{at}ua.ac.be

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 µg/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)- secretion after 8 days. Exposure to 60 µg/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- secretion and proliferation (P<0.001). DC activation was concentration-dependent and detected from 2 µg/mL CRP; the maximum effect was equivalent to that seen with 0.1 µg/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.

C-reactive protein (CRP), a predictor of cardiovascular disease (CVD), was tested as modulator of dendritic cells (DCs). Exposure to CRP induced DC activation, DC-mediated T-cell proliferation, and IFN- production. Immunohistochemistry could demonstrate DC/CRP colocalization in human plaques. This suggests that CRP in CVD patients can influence DC function during atherogenesis.

Key Words: C-reactive protein • dendritic cells • atherosclerosis • cell culture • immunohistochemistry

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