Human C-reactive protein activates monocyte-derived dendritic cells and induces dendritic cell-mediated T-cell activation.
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.


RESULTS
Human monocyte-derived immature DCs were cultured with human CRP (0 to 60 microg/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 microg/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 mug/mL CRP; the maximum effect was equivalent to that seen with 0.1 microg/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.
Van Vré
Emily A
EA
Department of Cardiology, University of Antwerp, B-2610 Wilrijk, Belgium. emily.vanvre@ua.ac.be
Bult
Hidde
H
Hoymans
Vicky Y
VY
Van Tendeloo
Viggo F I
VF
Vrints
Christiaan J
CJ
Bosmans
Johan M
JM
D000704:Analysis of Variance; D050197:Atherosclerosis / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000502:physiology*; D009000:Monocytes / Q000166:cytology; D011113:Polymyxins / Q000494:pharmacology; D011134:Polysaccharides / Q000494:pharmacology; D011336:Probability; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000166:cytology
D006684:HLA-DR Antigens; D011113:Polymyxins; D011134:Polysaccharides; D007371:Interferon-gamma; D002097:C-Reactive Protein