Complement mediates membrane rearrangements and lipogenesis (172.21)

Abstract

Abstract The complement is a major effector part in innate immunity. Its main biological function is to recognize foreign particles and macromolecules, and to promote their elimination either by opsonization or lysis. In order to avoid potential risk of host cells lysis, an efficient system of regulatory proteins is involved. Additional protective mechanisms include removal of membrane attacking complex by both vesicle shedding and internalization followed by exocytosis. The aim of research is to investigate alterations in membrane biogenesis and lipid biosynthesis in cells targeted by complement. Treatment of mouse NIH 3T3 fibroblasts with complement induces early and late phase responses. The early phase response is characterized by increase in intracellular Ca2+, alterations in phospholipid packing order and plasma membrane asymmetry, as well as translocation of lysosomal vesicles to the cell surface followed by activation of acid sphingomyelinase and ceramide production. We demonstrated that prestimulation of cells with sublityc complement doses followed by treatment with lytic concentrations substantially reduces levels of both plasma membrane-associated acid sphingomyelinase and ceramide, and protects cells from lysis. During late phase response we observed alterations in mRNA levels of several SREBP-targeted genes and lipid biosynthesis. Taken together, our data link regulated lipid dynamics and metabolism to acquired cell resistance to complement attack (accommodation).