COMPLEMENT C1Q INHIBITS CELLULAR SPREADING AND STIMULATES ADENYLYL-CYCLASE ACTIVITY OF FIBROBLASTS

C1q selectively localizes at injured tissues, where it may function as a regulator of cell-matrix interactions, We show here that purified C 1q, added to the culture medium of human gingival fibroblasts (HF) spr ead onto fibronectin substrates, elicited a round morphology that was accompanied by altered F-actin and correlated with inhibition of cellu lar spreading, Shape modification required integrity of the molecule a nd was specific, dose dependent, nontoxic, and reversible. Antispreadi ng activity was mediated, at least in part, by specific cell-surface C 1q receptors. We hypothesized that ligand occupancy of C1q receptors c ould influence shape by affecting intracellular levels of cyclic AMP ( cAMP). Within 20 min of exposure of adhering HF to C1q, we detected an increase in adenylyl cyclase activity (six-to ninefold) in cAMP accum ulation (by 20%) and in cAMP-dependent protein kinase activity (by 20% ). These changes suggested that the rounding effect of C1q may be asso ciated with activation of the adenylyl cyclase pathway. (C) 1998 Acade mic Press.