Effect of lipids, structural precursors of lipids and fatty acids on complement-mediated killing of antibody-sensitized nucleated cells

Abstract

The cytotoxic activity of limiting concentrations of human complement against antibody-sensitized line-10 guinea-pig hepatoma cells can be inhibited and/or enhanced by pretreatment of the complement with lipids and/or fatty acids. Cardiolipin (CL), phosphatidylglycerol (PG), phosphatidylcholine (PC), phosphatidylserine (PS), sphingomyelin (SPHMY), cholesterol (CHOL), cholesteryl oleate (CHOL-O), phosphatidic acid (PA) or mammalian phosphatidylethanolamine (PE m) were effective in inhibiting C activity. Bacterial phosphatidylethanolamine (PE b) had no effect. Several cholesteryl esters and triglycerides of known fatty acid composition were tested. CHOL-O and glyceryl-1, 2-stearate-3-oleate were effective, but cholesteryl palmitate, stearate, arachidonate and glyceryl-1, 3-stearate-2-oleate were not effective in inhibiting HuC action. Structural precursors of phosphoJipids effective in inhibiting HuC activity (e.g. l-α-glycerophosphoryl esters of choline, serine and ethanolamine) did not modify the action of HuC on antibody-sensitized line-10 cells under any conditions tested. In contrast to the larger mol. wt lipid, conditions were found in which fatty acid could inhibit or enhance the cytotoxic action of C. The modification of C activity was dependent upon the specificity of the antibody used to sensitize the cells, the chain length, and the concentration of the fatty acid. The results suggest that the composition and possible subtle structural characteristics of lipids may play a role in influencing the functional activity of complement.