The terminal complement proteins C5b-9 augment binding of high density lipoprotein and its apolipoproteins A-I and A-II to human endothelial cells.
Terminal complement protein complexes C5b-9 have been found in human atherosclerotic lesions. Insertion of C5b-9 in the endothelial cell membrane alters permeability, induces membrane vesiculation, and activates secretion. We hypothesized that complement might also alter interactions of the endothelial surface with lipoproteins, particularly high density lipoprotein (HDL), which is reported to inhibit C5b-9-induced hemolysis. We now demonstrate that exposure to C5b-9 increases (by 2- to 50-fold) specific binding of HDL and its apolipoproteins (apo) A-I and A-II to endothelial cells. Binding to cells exposed to antibody, C5b67, and C5b-8 was virtually unchanged. Enhanced binding was also dependent on the number of C5b-9 complexes deposited on the cells. Other agonists that activate endothelial secretion did not augment binding. Calcium was required for full exposure of new binding sites by C5b-9. The C5b-9-induced increase in binding was independent of the increase observed after cholesterol loading. In addition, apo A-I and A-II appear to compete for the same binding sites on untreated and C5b-9-treated cells. In contrast to the data reported for red cells, we were unable to detect significant inhibition of C5b-9-mediated endothelial membrane permeabilization by HDL (up to 1 mg/ml) or by apo A-I (up to 100 micrograms/ml). These data demonstrate that the C5b-9 proteins enhance endothelial binding of HDL and its apoproteins, suggesting that intravascular complement activation may alter cholesterol homeostasis in the vessel wall.
Hamilton
K K
KK
Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
Sims
P J
PJ
D016632:Apolipoprotein A-I / Q000378:metabolism* / Q000494:pharmacology; D016633:Apolipoprotein A-II / Q000378:metabolism* / Q000494:pharmacology; D001161:Arteriosclerosis / Q000209:etiology; D001665:Binding Sites; D001667:Binding, Competitive; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000502:physiology*; D003594:Cytoplasmic Granules / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism* / Q000494:pharmacology
D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D015938:Complement Membrane Attack Complex; D008075:Lipoproteins, HDL; D002784:Cholesterol; D002118:Calcium