Dendritic cells in the arterial wall express C1q: potential significance in atherogenesis.
OBJECTIVE
Dendritic cells (DCs) accumulate in atherosclerotic lesions but their characteristics and their role in atherogenesis are poorly understood. C1q, an element of the first component of complement, is expressed by interdigitating dendritic cells and follicular dendritic cells in the spleen. It has been suggested that C1q is involved in capturing immune complexes in the lymphoid tissue. Immune complexes are also detected in atherosclerotic lesions. The present study investigated whether C1q is expressed by DCs in the arterial wall. Because DCs accumulating within atherosclerotic lesions might originate from monocytes that infiltrate the intima from very early stages of atherosclerosis, C1q expression was also examined in monocyte-derived DCs in vitro.


METHODS
Specimens of the aorta, carotid, mammary, popliteal and tibial arteries were obtained during operation. Expression of C1q in the arterial wall was studied by immunohistochemistry. The nature of cells expressing C1q was studied in sections double stained with antibodies to C1q and cell type specific markers including CD1a and S-100 (for identification of DCs), CD68 (macrophages), CD3 (T-cells), von Willebrand factor (endothelial cells), and smooth muscle alpha-actin (smooth muscle cells). In vitro, DCs were differentiated from human peripheral blood monocytes using GM-CSF and IL-4. Peripheral blood monocytes were differentiated to macrophages using M-CSF. The expression of C1q in monocytes and in vitro monocyte-derived DCs and macrophages was determined by RT-PCR, Western blotting, immunofluorescence microscopy and flow cytometry.


RESULTS
In all the arterial specimens studied, DCs expressing C1q were detected. C1q was also found in macrophages, macrophage foam cells and in neovascular endothelial cells in atherosclerotic lesions, but no C1q expression was detected in T-cells and smooth muscle cells. In vitro analysis demonstrated that monocyte-derived DCs and macrophages express C1q but no C1q was detected in monocytes.


CONCLUSIONS
C1q is expressed by DCs residing in the arterial wall as well as by monocyte-derived DCs in vitro. Expression of C1q occurs during differentiation of monocytes to DCs and macrophages and might be important in binding and trapping immune complexes in atherosclerotic lesions.
Cao
Weiping
W
National University Medical Institutes, National University of Singapore, Blk MD11, #02-01 10 Medical Drive, Singapore 117597, Singapore.
Bobryshev
Yuri V
YV
Lord
Reginald S A
RS
Oakley
Reida E I
RE
Lee
Szu H
SH
Lu
Jinhua
J
D000199:Actins / Q000032:analysis; D000936:Antigen-Antibody Complex; D001011:Aorta; D001161:Arteriosclerosis / Q000276:immunology*; D002339:Carotid Arteries; D002478:Cells, Cultured; D015922:Complement C1q / Q000032:analysis*; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D005487:Foam Cells / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008264:Macrophages / Q000276:immunology; D008323:Mammary Arteries; D018613:Microscopy, Confocal; D011150:Popliteal Artery; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016909:Tibial Arteries; D017539:Tunica Intima / Q000276:immunology*
D000199:Actins; D000936:Antigen-Antibody Complex; D015922:Complement C1q