Expression of gC1q-R/p33 and its major ligands in human atherosclerotic lesions.
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.
Peerschke
Ellinor I B
EI
Department of Pathology, Weill Medical College of Cornell University, 525 East 68th Street, Room F715, New York, NY 10021, USA. epeersch@mail.med.cornell.edu
Minta
Joe O
JO
Zhou
Sonya Z
SZ
Bini
Alessandra
A
Gotlieb
Avrum
A
Colman
Robert W
RW
Ghebrehiwet
Berhane
B
D001161:Arteriosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002339:Carotid Arteries / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D011951:Receptors, Complement / Q000096:biosynthesis / Q000235:genetics*
D008024:Ligands; D008562:Membrane Glycoproteins; D011951:Receptors, Complement; C032402:complement 1q receptor