A role for anti-inflammatory agents and cyclic AMP in regulating fibronectin-mediated phagocytosis

The present study deals with the effects of anti-inflammatory drugs and agents known to elevate intracellular levels of cyclic AMP (cAMP) on plasma fibronectin-mediated (PFn) phagocytosis of radiolabeled, gelatin-coated latex particles (g-Ltx*) by inflammatory macrophages. Monolayers of casein-elicited peritoneal macrophages were preincubated with the specified agents for either 1 or 24 hrs at 37 degrees C prior to the measurements of phagocytosis in the presence of human plasma fibronectin (47 microgram/ml) and heparin (6.7 U/ml). Under these conditions, prostaglandin E1, colchicine, vincristine, and cytochalasin B were all effective in inhibiting g-Ltx* phagocytosis by macrophages in a dose-dependent fashion. More potent inhibition of phagocytosis was manifested by agents known to increase intracellular levels of cAMP in phagocytic cells. Dibutyryl cyclic AMP (dbcAMP), d,1-isoproterenol and aminophylline (10(-5) to 10(-3) M) were all effective in reducing the uptake of g-Ltx* by macrophages. The combination of dbcAMP and aminophylline acted additively. These studies demonstrate that anti-inflammatory drugs and cAMP-elevating agents exert potent inhibitory effects on fibronectin-mediated phagocytosis of gelatin-coated particles by macrophages. Thus, our system provides a suitable in vitro model for further investigations into the humoral regulation of phagocytosis of denatured collagen-coated particles and tissue debris by inflammatory phagocytic cells.