Role of C5a in the induction of tumoricidal activity in C3H/HeJ (Lps(d)) and C3H/OuJ (Lps(n)) macrophages

M. M. Hogan, K. B. Yancey, S. N. Vogel

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Thioglycollate-elicited macrophages from C3H/HeJ (Lps(d)) and C3H/OuJ (Lps(n)) mice were cultured in a two-signal, tumoricidal assay using recombinant interferon-γ (rIFN-γ) as the 'priming' signal and recombinant human C5a (rC5a) as the 'trigger' signal. These experiments were compared directly with a well established, two-signal tumoricidal assay in which rIFN-γ was used as the 'priming' signal and protein-rich, butanol-extracted lipopolysaccharide (But-LPS) as the 'trigger' signal. These studies showed that rIFN-α-primed macrophages can be triggered in a dose-dependent manner by rC5a to effect high levels of tumoricidal activity. Maximum levels of cytotoxicity achieved using this endogenously produced, biologically active peptide as a 'trigger' signal were comparable to those obtained using But-LPS. Moreover, experiments in which anti-C5 antibody was included in macrophage cultures stimulated with rIFN-γ and But-LPS showed a significant reduction (P < .05) in tumoricidal activity. Because LPS has been shown to induce macrophage C5 production and enzyme release, these findings suggest that macrophage-derived C5 is locally converted to C5a (or some other biologically active C5 cleavage fragment), which functions as an autocrine trigger signal for the induction of tumoricidal activity. In summary, these data suggest 1) that rC5a can provide a 'second signal' to rIFN-γ-primed murine macrophages for the induction of tumoricidal activity and 2) that macrophage-derived C5 or C5a may represent an autocrine signal induced by exogenous 'trigger signals.'

Original languageEnglish (US)
Pages (from-to)565-570
Number of pages6
JournalJournal of Leukocyte Biology
Volume46
Issue number6
DOIs
StatePublished - Jan 1 1989

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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