The Journal of Immunology, Vol 155, Issue 5 2614-2619, Copyright © 1995 by American Association of Immunologists

ARTICLES

Murine mast cells express two types of C1q receptors that are involved in the induction of chemotaxis and chemokinesis

B Ghebrehiwet, RR Kew, BL Gruber, MJ Marchese, EI Peerschke and KB Reid
Department of Medicine, State University of New York, Stony Brook 11794, USA.

Although previous studies have shown that different cells and cell lines of murine origin bind human C1q, suggesting that they display cell surface receptors for C1q, no information is available to indicate whether mouse or human mast cells express C1q receptors. This paper presents the first evidence to show that murine mast cells express specific receptors for C1q. Western blot analysis of cell membrane proteins prepared from a bone marrow-derived mouse cell line using two monospecific 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 "heads" 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 specific and dose-dependent manner. Interestingly, the C1q-induced migratory response was found to be biphasic; the first response peaked at a C1q concentration of 0.1 nM, whereas the second phase peaked at approximately 40 nM. Checkerboard analysis of the mast cell migratory response to C1q showed that the first phase was primarily due to chemotaxis and the second phase was attributable to chemokinesis. Preincubation of C1q with Abs specific for the collagen-like tail of the molecule abolished both its chemotactic and chemokinetic response, whereas heat inactivation of C1q (56 degrees C, 1 h) resulted in 85% abrogation of the chemotactic phase and 42% reduction in the chemokinetic phase. The observed mast cell migratory responses were mediated by cell surface C1q-R(s), as inclusion of a mixture of anti- C1q-R and anti-gC1q-R Abs with the cells inhibited their migratory response toward C1q. However, incubation of cells with various doses of C1q did not result in histamine release. Furthermore, engagement of mast cell C1q-Rs by the ligand C1q induced an antiproliferative response, as coculturing of mast cells with C1q resulted in a specific and dose-dependent decrease in DNA synthesis. These data suggest that C1q-Rs may play a significant role in mast cell function and regulation by providing an important signal through which mast cells can be recruited to inflammatory sites of increased C1q concentration.

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