MURINE MAST-CELLS EXPRESS 2 TYPES OF C1Q RECEPTORS THAT ARE INVOLVED IN THE INDUCTION OF CHEMOTAXIS AND CHEMOKINESIS

Although previous studies have shown that different cells and cell lin es of murine origin bind human C1q, suggesting that they display cell surface receptors for C1q, no information is available to indicate whe ther mouse or human mast cells express C1q receptors. This paper prese nts the first evidence to show that murine mast cells express specific receptors for C1q. Western blot analysis of cell membrane proteins pr epared from a bone marrow-derived mouse cell line using two monospecif ic polyclonal Abs, one directed against the 60-kDa C1q receptor (C1q-R ) that binds to the collagen-like stalk of C1q (cC1q-R) and the other directed against the 33-kDa molecule that binds to the globular ''head s'' of C1q (gC1q-R), show that both of these receptors are present on these cells. In addition, C1q can induce mast cell migration in a spec ific and dose-dependent manner. Interestingly, the C1q-induced migrato ry response was found to be biphasic; the first response peaked at a C 1q concentration of 0.1 nM, whereas the second phase peaked at approxi mately 40 nM. Checkerboard analysis of the mast cell migratory respons e to C1q showed that the first phase was primarily due to chemotaxis a nd the second phase was attributable to chemokinesis. Preincubation of C1q with Abs specific for the collagen-like tail of the molecule abol ished both its chemotactic and chemokinetic response, whereas heat ina ctivation of C1q (56 degrees C, 1 h) resulted in 85% abrogation of the chemotactic phase and 42% reduction in the chemokinetic phase. The ob served mast cell migratory responses were mediated by cell surface C1q -R(s), as inclusion of a mixture of anti-cC1q-R and anti-gC1q-R Abs wi th the cells inhibited their migratory response toward C1q. However, i ncubation of cells with various doses of C1q did not result in histami ne release. Furthermore, engagement of mast cell C1q-Rs by the ligand C1q induced an antiproliferative response, as coculturing of mast cell s with C1q resulted in a specific and dose-dependent decrease in DNA s ynthesis. These data suggest that C1q-Rs may play a significant role i n mast cell function and regulation by providing an important signal t hrough which mast cells can be recruited to inflammatory sites of incr eased C1q concentration.