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Cholesterol-Dependent Nonimmune Human Complement Activation Resulting in Damage to Liposomes

Department of Immunology, Walter Reed Army Institute of Research, Washington, D.C. 20012

Abstract

Liposomes containing varying concentrations of cholesterol (CHOL) were prepared in order to investigate the role of CHOL in complement (C)-mediated immune damage. The liposomes were comprised of dipalmitoyllecithin, CHOL, dicetyl phosphate, and either contained or lacked galactocerebroside as antigen. At high concentrations of liposomal CHOL each of the preparations (either containing or lacking galactocerebroside) released trapped glucose spontaneously in C in the absence of antiserum. This did not occur at low concentrations of CHOL. This effect was observed in the presence of human C from 8 of 12 individuals studied, but was not found with guinea pig C. It was eliminated after inactivation of C by a) preheating the serum at 56° for 30 min, b) addition of Mg₂EDTA, or c) preabsorbing the serum with immune complexes (egg albuminanti egg albumin). Furthermore, preabsorbing the serum with high CHOL liposomes caused a drop in the hemolytic C titer, whereas low CHOL liposomes did not affect the hemolytic titer.