0000000000298201
AUTHOR
Paul S. Seifert
Isolation and characterization of a complement-activating lipid extracted from human atherosclerotic lesions.
The major characteristics of human atherosclerotic lesions are similar to those of a chronic inflammatory reaction, namely fibrosis, mesenchymal cell proliferation, the presence of resident macrophages, and cell necrosis. Atherosclerosis exhibits in addition the feature of lipid (mainly cholesterol) accumulation. The results of the present report demonstrate that a specific cholesterol-containing lipid particle present in human atherosclerotic lesions activates the complement system to completion. Thus, lipid could represent a stimulatory factor for the inflammatory reaction, whose underlying mechanistic basis may be, at least in part, complement activation. The complement-activating lipid …
The apolipoprotein(a) moiety of lipoprotein(a) interacts with the complement activation fragment iC3b but does not functionally affect C3 activation or degradation
A previous study has shown that complement component C3 binds to recombinant apolipoprotein(a) (r-apo(a)). In the present report we have investigated the interactions between lipoprotein(a) (Lp(a)), r-apo(a) and C3 in relation to complement activation and degradation. Neither Lp(a) nor r-apo(a) affected complement activation as indicated by sheep and rabbit red blood cell hemolytic assays, and by assessment of the amount of C3a generated in zymosan-activated human serum in the presence or absence of Lp(a). Crossed immunoelectrophoretic analyses indicated that Lp(a) retarded the migration of iC3b in complement-activated serum but had no effects on C3, C3b, C3c or C3dg. Recombinant apo(a) exh…
The Participation of the Complement System in Atherosclerotic Vascular Disease
Atherosclerosis is a vascular disease of large and medium-sized arteries wherein the tunica intima becomes thickened due to lipid accumulation, mostly cholesterol and its esters, smooth muscle cell proliferation, and increased deposition of connective tissue matrix. A major risk factor in the development of this disease is hypercholesterolemia arising from elevated levels of low density lipoproteins (LDL). The earliest recognizable lesion, which may be a precursor to the fibrofatty plaque, is the fatty streak. It is predominantly composed of monocyte-derived macrophage foam cells, i.e. cells ladened with intracellular lipid droplets. Hence, a fundamental aspect of atherogenesis is the insud…
Analysis of complement C3 activation products in human atherosclerotic lesions.
Abstract Cleavage of the complement C3 protein is essential for complement activation. Saline extracts of human atherosclerotic lesions were examined by various techniques for the presence of C3 cleavage fragments. Crossed intermediate gel immunoelectrophoresis revealed that native C3 was the predominate C3 protein in extracts and that the C3dg fragment was also detected. SDS-PAGE/ Western blot analyses of lesion extracts employing monoclonal antibodies directed at C3c and C3dg fragment determinants demonstrated molecular weight bands corresponding to the known molecular weights of all the physiologic C3 cleavage fragments, except Cab which is known to have a short half-life. After C3, the …