| First Author | Hogan MM | Year | 1989 |
| Journal | J Leukoc Biol | Volume | 46 |
| Issue | 6 | Pages | 565-70 |
| PubMed ID | 2509612 | Mgi Jnum | J:24638 |
| Mgi Id | MGI:72373 | Doi | 10.1002/jlb.46.6.565 |
| Citation | Hogan MM, et al. (1989) Role of C5a in the induction of tumoricidal activity in C3H/HeJ (Lpsd) and C3H/OuJ (Lpsn) macrophages. J Leukoc Biol 46(6):565-70 |
| abstractText | Thioglycollate-elicited macrophages from C3H/HeJ (Lpsd) and C3H/OuJ (Lpsn) mice were cultured in a two-signal, tumoricidal assay using recombinant interferon-gamma (rIFN-gamma) 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-gamma was used as the priming signal and protein-rich, butanol-extracted lipopolysaccharide (But-LPS) as the trigger signal. These studies showed that rIFN-gamma-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-gamma and But-LPS showed a significant reduction (P less than .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-gamma-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. |
