title: Molecular regulation of phagocyte function. Evidence for involvement of a guanosine triphosphate-binding protein in opsonin-mediated phagocytosis by monocytes.
abstract: Although many functions of phagocytes are known to be regulated by guanosine triphosphate (GTP)-binding proteins, phagocytosis itself has not been considered one of these. However, previous studies have examined only unstimulated neutrophil phagocytosis. Motivated by our previous work, which showed that stimulated neutrophil phagocytosis is regulated by GTP-binding proteins (H. D. Gresham, M. G. Peters, and E. J. Brown. 1986. J. Cell Biol. 103:215a), we have examined the effect of pertussis toxin (PT) on monocyte receptor-mediated phagocytosis. PT inhibited unstimulated and fibronectin-stimulated IgG-mediated phagocytosis and also inhibited C3b-mediated phagocytosis stimulated by fibronectin or phorbol dibutyrate. Cholera toxin (CT) had no effect on unstimulated or stimulated phagocytosis mediated by IgG or C3b. PT inhibition of phagocytosis was not mediated via increases in cellular cAMP levels or by inhibition of the respiratory burst. Inhibition of phagocytosis did not result from decreased numbers of plasma membrane opsonin receptors nor decreased ability to bind opsonized targets. Although phorbol ester-stimulated phagocytosis was inhibited by PT, ligand-independent internalization of CR1 stimulated by phorbol dibutyrate proceeded normally in PT-intoxicated cells. We conclude that a PT-sensitive GTP-binding protein does regulate phagocytic function in monocytes. This protein operates on a molecular mechanism specific to the process of ingestion in both unstimulated monocytes and in cells stimulated to increase phagocytosis. Because unstimulated neutrophil phagocytosis is unaffected by PT or CT, and stimulated neutrophil phagocytosis is inhibited by both PT and CT, our data also demonstrate that monocytes and neutrophils have distinct mechanisms for regulation of phagocytic function.
mesh_terms: D002374:Catalase / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D003179:Complement C3b / Q000502:physiology; D005353:Fibronectins / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology; D009895:Opsonin Proteins / Q000502:physiology; D037342:Pertussis Toxin; D010587:Phagocytosis / Q000187:drug effects; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology; D011961:Receptors, Fc / Q000502:physiology; D013482:Superoxide Dismutase / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D005353:Fibronectins; D009895:Opsonin Proteins; D010703:Phorbol Esters; D011961:Receptors, Fc; D010566:Virulence Factors, Bordetella; D015240:Phorbol 12,13-Dibutyrate; D003179:Complement C3b; D002772:Cholera Toxin; D002374:Catalase; D013482:Superoxide Dismutase; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins