Interaction of C-reactive protein with liposomes. III. Membrane requirements for binding.
We have previously presented a model for CRP-membrane interactions using liposomes composed of dimyristoyl phosphatidylcholine (DMPC), cholesterol (CHOL), stearylamine (SA), and galactosyl ceramide. We have shown that the interaction of cRP with these liposomes in the presence of human serum results in consumption of hemolytic C and membrane lysis. In the present paper we have directly examined the binding reaction between CRP and liposomes using radiolabeled CRP. We have found that this binding is more characteristic of CRP interactions with polycations than CRP interactions with phosphocholine- (PC) containing molecules. CRP binding to liposomes was dependent on the presence of SA in the membrane and could occur with dimyristoyl phosphatidylethanolamine in place of DMPC. The binding was not inhibited by ethylenediaminetetraacetate (EDTA) but could be inhibited by CaCl2, whereas CRP binding to PC-Sepharose was inhibited by EDTA and required CaCl2. We have further examined the effects of changes in membrane composition on CRP binding to liposomes. In liposomes with a limiting density of SA, we found increased CRP binding with changes in composition that would increase membrane fluidity. In most cases, the amount of CRP binding correlated with the amount of C activation observed previously. However, increasing the amount of CHOL in the membrane was found to increase C activation while decreasing CRP binding. These findings indicate that CRP binding to membranes and subsequent C activation can occur through cationic molecules as well as phospholipids.
D000588:Amines / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002097:C-Reactive Protein / Q000378:metabolism*; D002784:Cholesterol / Q000494:pharmacology; D004134:Dimyristoylphosphatidylcholine; D005699:Galactosylceramides / Q000494:pharmacology; D006801:Humans; D008081:Liposomes / Q000378:metabolism*; D008566:Membranes; D051379:Mice; D010713:Phosphatidylcholines / Q000494:pharmacology
D000588:Amines; D005699:Galactosylceramides; D008081:Liposomes; D010713:Phosphatidylcholines; D002097:C-Reactive Protein; D002784:Cholesterol; C009317:stearylamine; D004134:Dimyristoylphosphatidylcholine