Complement subcomponent C1q modulation of TNF-alpha binding to L929 cells for enhanced TNF-mediated cytotoxicity.

Complement subcomponent C1q has been recently implicated in the modulation of autocrine binding of TNF-alpha to murine macrophages for induction of nitric oxide synthase. In the present study, the putative role of C1q in increasing TNF-alpha binding to L929 cells to mediate cytotoxicity was explored. TNF-sensitive L929 cells (L929-S) had higher total endogenous cellular and surface C1q levels and bound correspondingly more phycoerythrin-labelled rTNF-alpha (PE-TNF) than did a TNF-resistant L929 variant (L929-R). Pretreatment of L929-S with soluble C1q increased their sensitivity to TNF-mediated cytotoxicity coincident with increased binding of PE-TNF, but similar treatment of L929-R had no effect. Pretreatment of L929-S with an inhibitor of C1q secretion, 3,4 dehydro-D,L-proline (DHP), resulted in a decrease in their TNF-mediated cytotoxicity, as well as reduced binding of PE-TNF. Subsequent exposure of DHP-treated L929-S with exogenous soluble C1q restored their TNF-mediated cytotoxicity and binding of PE-TNF. These results provide evidence for the modulation of TNF-alpha binding to TNF sensitive tumour targets L929 by either endogenously synthesized or exogenously added C1q to promote TNF-mediated cytotoxicity by mechanisms which remain to be elucidated.