A growing body of evidence supports the hypothesis that
atherosclerosis has an inflammatory component, and that immune mechanisms, including complement activation, are likely to be involved. gC1q-R/p33 (gC1q-R) is a multifunctional and multicompartmental cellular
protein, which is postulated to play a role in
inflammation and
thrombosis by interacting with C1q and
high molecular weight kininogen (HK). To examine the expression of gC1q-R and its major
ligands, C1q and HK, in human atherosclerotic lesions, sections of carotid arteries removed during
endarterectomy and coronary arteries obtained at autopsy were stained with specific polyclonal or
monoclonal antibodies. Control sections were stained with irrelevant rabbit
IgG or isotype matched murine
monoclonal antibody (MOPC), respectively. Tissue sections were counterstained with
hematoxylin and examined by light microscopy. Specific staining for gC1q-R, C1q, and HK was observed in and around atherosclerotic lesions. In contrast to control
antibodies,
antibodies directed against gC1q-R reacted with endothelial cells, foam cells, smooth muscle cells, and inflammatory cells present in the intima and media of atherosclerotic lesions. In addition, the necrotic central core of advanced lesions with calcifications,
fibrin, and
lipids, stained intensely for gC1q-R, and negligibly with control
antibodies. HK demonstrated a similar staining pattern, whereas C1q was most heavily expressed in the fibrous cap and necrotic core of atherosclerotic lesions. The localization of gC1q-R and its
ligands C1q and HK in atherosclerotic lesions, and the previously described ability of gC1q-R to modulate
complement,
kinin, and coagulation cascades, suggest that gC1q-R may play an important role in promoting
inflammation and
thrombosis in atherosclerotic lesions.