Chemotactic factor-induced generation of superoxide radicals by human neutrophils: evidence for the role of sodium.
The role of sodium ion in superoxide (O2-) generation by human peripheral neutrophils was investigated. Cells were activated by exposure to the synthetic tripeptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP), and O2- release was assessed by ferricytochrome c reduction after 5 min of incubation at 37 degrees C in the presence of FMLP 4 X 10(-8) M. In the absence of monovalent cations (isotonic glucose), negligible O2- generation occurred. There was a progressive increase in the magnitude of FMLP-induced O2- generation with increasing Na+ concentration up to 90 mM, where the response was noted to plateau. Varying the K+ concentration (1 to 10 mM) had no effect on the amount of O2- produced in the presence of Na+ 140 mM. FMLP also stimulated 22Na+ and 48Ca2+ uptake by the cells in a dose- and time-dependent fashion. FMLP-induced 22Na+ uptake appeared to be independent of the external Ca2+ concentration ( to 4 mM). In contrast, there was a progressive decrease in themagnitude of the FMLP-induced increase in 45Ca2+ uptake as the Na+ concentration was reduced by replacement with choline+ or glucose. These studies support a requirement for Na+ in FMLP-induced O2- generation and suggest that a Na+ influx may underlie the nature of this requirement. The data are also consistent with the hypothesis that a Na+ influx may precede the Ca2+ influx in the FMLP-induced activation sequence.
D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002414:Cations, Monovalent; D002630:Chemotactic Factors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D009239:N-Formylmethionine / Q000031:analogs & derivatives / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology*; D009842:Oligopeptides / Q000494:pharmacology; D010100:Oxygen / Q000096:biosynthesis*; D010649:Phenylalanine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D013481:Superoxides / Q000096:biosynthesis*
D002414:Cations, Monovalent; D002630:Chemotactic Factors; D009842:Oligopeptides; D013481:Superoxides; D009239:N-Formylmethionine; D010649:Phenylalanine; D012964:Sodium; D011188:Potassium; D010100:Oxygen; D002118:Calcium