Defective Fc-mediated phagocytosis in C3H/HeJ macrophages. II. Correction by cAMP agonists.
Peritoneal macrophages from LPS hyporesponsive C3H/HeJ mice lose the capacity to bind and phagocytose opsonized sheep erythrocytes (EA) over a 48-hr culture period. This loss in Fc receptor capacity is markedly different from the progressive increase in phagocytic ability exhibited by cultured macrophages derived from LPS-responsive C3H/HeN mice. Since dibutyryl-cyclic adenosine monophosphate (DBcAMP) has previously been reported to modulate membrane receptor expression in lymphocytes and certain macrophage-like cell lines, we examined its effects on EA binding and phagocytosis by C3H/HeJ macrophages. DBcAMP not only reverses the binding defect in C3H/HeJ macrophages but also restores EA phagocytosis to the level of control C3H/HeN cultures. 8-Bromo-cAMP, as well as other agents known to elevate intracellular cAMP (i.e., isoproterenol plus isobutylmethylxanthine or prostaglandin E2) also corrected the phagocytic defect. Since the C3H/HeJ macrophage phagocytic defect can also be reversed by in vitro stimulation with a lymphokine-rich culture supernatant, we examined the effect of this treatment on intracellular cAMP levels. Lymphokine treatment produced a 60% increase in the levels of macrophage intracellular cAMP. These findings suggest that the C3H/HeJ differentiation defect may be secondary to some abnormality in a cAMP dependent pathway.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D000242:Cyclic AMP / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005260:Female; D007141:Immunoglobulin Fc Fragments; D007213:Indomethacin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008222:Lymphokines / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D010587:Phagocytosis; D011458:Prostaglandins E / Q000494:pharmacology
D007141:Immunoglobulin Fc Fragments; D008222:Lymphokines; D011458:Prostaglandins E; D003208:Concanavalin A; D003994:Bucladesine; D000242:Cyclic AMP; D007545:Isoproterenol; D007213:Indomethacin