Role of different Ca2+ sources in the superoxide production of human neutrophil granulocytes

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Abstract

The role of different Ca2+ sources in the activation of the NADPH oxidase was investigated in human neutrophil granulocytes. Selective depletion of the stimulus-responsive intracellular Ca2+-pool and the consequent opening of the store-dependent Ca2+ channel of the plasma membrane was achieved with thapsigargin, an inhibitor of microsomal Ca2+- ATPase. Low concentration (10-100 nM) of thapsigargin did not induce any O2--production, indicating that elevation of [Ca2+](ic) to similar level and probably via similar route as following stimulation of chemotactic receptors, by itself is not sufficient to activate the NADPH oxidase. In significantly higher concentration (1-10 μM) thapsigargin did induce O2-generation but this effect was not the result of elevation of [Ca2+](ic). In the absence of external Ca2+ a gradual decrease of the responsive Ca2+ pool was accompanied by a gradual decrease of the rate and duration of the respiratory response stimulated by formyl-methionyl-leucyl- phenylalanin. Maximal extent of receptor-initiated O2--production could only be obtained when the intracellular [Ca2+] was higher than the resting level. Under this condition Ca2+ originating from intracellular or external source was equally effective in supporting the biological response.

Original languageEnglish
Pages (from-to)1092-1099
Number of pages8
JournalFree Radical Biology and Medicine
Volume26
Issue number9-10
DOIs
Publication statusPublished - May 1 1999

Keywords

  • Calcium
  • Capacitative calcium influx
  • Free radicals
  • NADPH oxidase
  • Neutrophils
  • Superoxide
  • Thapsigargin

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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