Evidence for Endogenous C1q Modulates TNF-α Receptor Synthesis and Autocrine Binding of TNF-α Associated with Lipid A Activation of Murine Macrophages for Nitric Oxide Production

The role of endogenously synthesized complement subcomponent C1q on autocrine binding of tumor necrosis factor-α (TNF-α) and on TNF-α receptor (TNF-R) mRNA synthesis by mouse macrophages was investigated. Activation of C3H mouse peritoneal macrophages (C3H-PMφ) by Lipid A induced TNF-α and nitric oxide (NO) to kill tumor targets. Such activation also increased macrophage-endogenous C1q synthesis and secretion in a dose-dependent fashion. Antibody for C1q markedly inhibited C3H-PMφ NO production in response to Lipid A, but had no effect on TNF-α production. C3H-PMφ treated with C1q or Lipid A displayed increased TNF-R mRNA synthesis and in combination with Lipid A and anti-C1q antibody inhibited TNF-R and nitric oxide synthase (NOS) mRNA synthesis compared with Lipid A only, but had no effect on TNF mRNA synthesis.In vitrotreatment of C3H-PMφ with C1q also increased TNF-α binding to their surfaces. Taken together, the data indicate that endogenously synthesized C1q is operative in promoting TNF-R mRNA synthesis and resultant autocrine binding of TNF-α for induction of NOS in the process of NO-mediated tumor cytotoxicity by Lipid A-activated macrophages.