title: A guanine nucleotide regulatory protein controls polyphosphoinositide metabolism, Ca2+ mobilization, and cellular responses to chemoattractants in human monocytes.
abstract: Previous studies demonstrated that oligopeptide chemoattractant receptors on PMN and macrophages exist in high and low affinity states which are interconvertible by guanosine di- and triphosphates. These observations suggest that guanine nucleotide regulatory (N) proteins play a role in phagocyte activation by chemotactic factors. The data presented here indicate that chemotactic factor receptors on monocytes utilize an N protein to activate phospholipase C and subsequent biologic responses by the cells. This conclusion is based on the findings that inactivation of an N protein of 41,000 m.w. by Bordetella pertussis toxin (PT) treatment abolishes monocyte responsiveness to chemoattractants but not to lectins, PMA, or the Ca2+ ionophore A23187. Treatment with PT inhibited IP3 production, Ca2+ mobilization, and cellular activation as assessed by chemotaxis and changes in forward light scattering in response to the chemoattractants by at least 80%. Therefore, a PT-sensitive N protein plays an important role in the activation of monocytes by chemoattractants.
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002630:Chemotactic Factors / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000502:physiology*; D006801:Humans; D009000:Monocytes / Q000378:metabolism* / Q000502:physiology; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D002630:Chemotactic Factors; D010716:Phosphatidylinositols; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D002118:Calcium