title: Superoxide generation and granule enzyme release induced by ionophore A23187. Studies on the early events of neutrophil activation.
abstract: The responses of isolated human peripheral neutrophils to activation by the divalent cation ionophore A23187 (4 x 10(-8) M to 2 x 10(-5) M) were studied over the course of 15 min at 37 degrees C. Dose-dependent increases were noted in the following A23187-induced functions: (1) membrane depolarization, as assessed by a fluorescent cyanine dye, (2) altered membrane permeability to 22Na+ and 45Ca2+, (3) increased intracellular levels of cAMP, (4) O2-generation, and (5) granule enzyme release. Membrane depolarization and the cAMP response preceded the onset of O2- generation and exocytosis, which began after a latency period of approximately 30 sec. All five functions induced by 2 x 10(-5) M A23187 required approximately 1 mM Ca0 for optimal expression and declined substantially as Ca0 was reduced towards a nominal O mM. In contrast, the Na+ ionophore gramicidin D (0.1 to 10 microgram/ml) caused cell depolarization and increased 22Na+ ionophore gramicidin D (0.1 to 10 microgram/ml) caused cell depolarization and increased 22Na+ uptake but did not stimulate 45Ca2+ uptake, the cAMP response, O2- generation, or exocytosis of granule constituents. The observations dissociate membrane depolarization and altered Na+ permeability, on the one hand, from a Ca2+ influx, cAMP response, O2- release, and exocytosis on the other. These studies, then, are consistent with a hypothesis that a Ca2+ influx is required for the biologic expressions of cell activation.
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D006152:Cyclic GMP / Q000096:biosynthesis; D003594:Cytoplasmic Granules / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D006096:Gramicidin / Q000494:pharmacology; D006801:Humans; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000502:physiology*; D010100:Oxygen / Q000096:biosynthesis*; D012964:Sodium / Q000378:metabolism; D013481:Superoxides / Q000096:biosynthesis*; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D013481:Superoxides; D006096:Gramicidin; D000001:Calcimycin; D012964:Sodium; D000242:Cyclic AMP; D006152:Cyclic GMP; D010100:Oxygen; D002118:Calcium