The NADPH oxidase of human polymorphonuclear leukocytes. Evidence for regulation by multiple signals.

Journal Article (Journal Article)

Activation of the membrane-bound NADPH oxidase in human polymorphonuclear leukocytes can be triggered by chemoattractants, the tumor promoter phorbol myristate acetate or the calcium ionophore A23187. We have shown previously that these stimuli have markedly different temporal patterns of oxidase activation (McPhail, L. C., and Snyderman, R. (1983) J. Clin. Invest. 72, 192-200), suggesting that each follows, at least in part, a unique transductional pathway. We now report that if leukocytes were sequentially exposed to any of several combinations of heterologous stimuli, the pattern of activation by the second stimulus was strikingly altered, resulting in a more rapid rate and enhanced level of oxidase activation by the second stimulus. This suggests that exposure of cells to the first stimulus (priming) had influenced an intermediate also used by the second stimulus. The signal for priming could be clearly distinguished from the signal causing oxidase activation by the dose-response curves for each, as well as by the use of several pharmacologic agents. In addition, if leukocytes were given sequential doses of homologous stimuli, either partial (phorbol myristate acetate) or full (N-formyl-methionyl-leucyl -phenylalanine and A23187) desensitization of oxidase activation was observed. These results demonstrate that these stimuli share a common intermediate in the pathway of oxidase activation. Moreover, the data indicate that NADPH oxidase activation is regulated by at least three distinct signals: signal 1 (priming), signal 2 (activation), and signal 3 (inactivation). It is likely that more than one intracellular messenger exerts a modulating influence on NADPH oxidase activity and that its regulation involves the interplay between several cellular control proteins.

Full Text

Duke Authors

Cited Authors

  • McPhail, LC; Clayton, CC; Snyderman, R

Published Date

  • May 10, 1984

Published In

Volume / Issue

  • 259 / 9

Start / End Page

  • 5768 - 5775

PubMed ID

  • 6425297

International Standard Serial Number (ISSN)

  • 0021-9258


  • eng

Conference Location

  • United States