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Complement Subcomponent C1q Modulation of TNF‐α Binding to L929 Cells for Enhanced TNF‐Mediated Cytotoxicity
Author(s) -
JIANG HONG,
ZHOU ANQIANG,
HERRIOTT M. J.,
RUMMAGE J. A.,
STEWART C. A.,
FAST D. J.,
LEU R. W.
Publication year - 1996
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.1992.d01-284.x
Subject(s) - cytotoxicity , tumor necrosis factor alpha , chemistry , biochemistry , cytokine , microbiology and biotechnology , pharmacology , in vitro , biology , immunology
Complement subcomponent C1q has been recently implicated in the modulation of autocrine binding of TNF‐α to murine macrophages for induction of nitric oxide synthase. In the present study, the putative role of C1q in increasing TNF‐α 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‐α (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‐α 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.