CLQ-MEDIATED CHEMOTAXIS BY HUMAN NEUTROPHILS - INVOLVEMENT OF GCLQR AND G-PROTEIN SIGNALING MECHANISMS

C1q, the first component of the classical pathway of the complement sy stem, interacts with various cell types and triggers a variety of cell -specific cellular responses, such as oxidative burst, chemotaxis, pha gocytosis, etc. Different biological responses are attributed to the i nteraction of C1q with more than one putative cell-surface C1q recepto r/C1q-binding protein. Previously, it has been shown that C1q-mediated oxidative burst by neutrophils is not linked to G-protein-coupled fMe t-Leu-Phe-mediated response. In the present study, we have investigate d neutrophil migration brought about by C1q and tried to identify the signal-transduction pathways involved in the chemotactic response. We found that C1q stimulated neutrophil migration in a dose-dependent man ner, primarily by enhancing chemotaxis (directed movement) rather than chemokinesis (random movement). This C1q-induced chemotaxis could be abolished by an inhibitor of G-proteins (pertussis toxin) and PtdIns(3 ,3,5)P-3 kinase (wortmannin and LY294002). The collagen tail of C1q ap peared to mediate chemotaxis. gC1qR, a C1q-binding protein, has recent ly been reported to participate in C1q-mediated chemotaxis of murine m ast cells and human eosinophils. We observed that gC1qR enhanced bindi ng of free C1q to adherent neutrophils and promoted C1q-mediated chemo taxis of neutrophils by nearly seven-fold. Our results suggests C1q-me diated chemotaxis involves gC1qR as well as G-protein-coupled signal-t ransduction mechanisms operating downstream to neutrophil chemotaxis.