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.
D000527:Alprostadil; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D003593:Cytoplasm / Q000187:drug effects; D005353:Fibronectins / Q000494:pharmacology*; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008297:Male; D010587:Phagocytosis / Q000187:drug effects*; D011458:Prostaglandins E / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000893:Anti-Inflammatory Agents; D005353:Fibronectins; D011458:Prostaglandins E; D003994:Bucladesine; D000242:Cyclic AMP; D000527:Alprostadil