Consequences of cell membrane attack by complement: release of arachidonate and formation of inflammatory derivatives.

TLDR

Complement activation of antibody‑sensitized tumor cells and macrophages hydrolyzes cellular phospholipids, releasing up to ~25 % of incorporated arachidonic acid and generating prostaglandins, thromboxane B₂, and hydroxyicosatetraenoic acids, with terminal components C6–C8 essential for the major release. The extent of arachidonic acid release parallels the cytolytic response, is markedly reduced by C6/C8 deficiency but restored by purified C6 or C8, and the data do not exclude a role for C9.

Abstract

Treatment of [3H]arachidonic acid [( 3H]C20:4)-labeled and antibody-sensitized Ehrlich ascites tumor cells with guinea pig or rabbit serum complement (C) released up to about 20 or 25% of the incorporated [3H]C20:4 into the aqueous phase as a consequence of C-induced hydrolysis of cellular phospholipid. The dose-response curve of release of [3H]C20:4 from Ehrlich ascites tumor cells, with respect to C, was approximately in the same range as the cytolytic response. In the case of [3H]C20:4-labeled and antibody-sensitized peritoneal mouse macrophages, treatment with C induced release of about 11% of the incorporated 3H as C20:4 and about 6% as prostaglandins, thromboxane B2, and hydroxyicosatetraenoic acids. C6- and C8-deficient rabbit and human sera, respectively, induced release of small amounts of [3H]C20:4 from Ehrlich ascites tumor cells and macrophages; these deficient sera also released traces of oxygenated derivatives from macrophages. Addition of purified C6 or C8 effectively restored release from both cell types, indicating that the terminal C proteins, up to and including C8, are required for the major part of the release. Our results do not rule out a possible requirement for C9.