Calcium signalling is altered in myeloid cells with a deficiency in NADPH oxidase activity

Clin Exp Immunol. 2003 Apr;132(1):53-60. doi: 10.1046/j.1365-2249.2003.02138.x.

Abstract

The relation of O(2.-)-production and Ca2+ homeostasis was investigated in PLB-985 cell lines and neutrophilic granulocytes from peripheral blood. In differentiated wild-type PLB-985 cells, a high level of O(2.-)-production was associated with a significant decrease in the membrane potential and the inhibition of capacitative Ca2+ entry. These correlations were not observed in gp91phox -/- cells or in cells transfected with a non-functional mutant of gp91phox (Thr341Lys). Membrane depolarization and inhibition of Ca2+ entry reappeared in cells transfected with wild-type gp91phox. These experiments demonstrate that inhibition of Ca2+ entry depends on the presence of a functional NADPH oxidase. The Ca2+ signal induced by stimulation of chemotactic receptors also showed remarkable differences: [Ca2+]ic in the sustained phase was higher in gp91phox-/- than in wild-type cells. Alteration of the Ca2+ signal was reproduced by treating peripheral blood neutrophils with the NADPH oxidase inhibitor diphenylene-iodonium. It is concluded that the deficiency in O(2.-)-production is accompanied by significant alterations of Ca2+ homeostasis in myeloid cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism
  • Calcium Signaling*
  • Cell Line
  • Cells, Cultured
  • Enzyme Inhibitors / pharmacology
  • Granulomatous Disease, Chronic / metabolism*
  • Humans
  • Leukemia, Promyelocytic, Acute
  • Manganese / metabolism
  • Membrane Potentials / drug effects
  • Myeloid Cells / metabolism*
  • NADPH Oxidases / deficiency*
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Onium Compounds / pharmacology
  • Superoxides / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Enzyme Inhibitors
  • Onium Compounds
  • Superoxides
  • Manganese
  • diphenyleneiodonium
  • Nitric Oxide Synthase
  • NADPH Oxidases
  • Tetradecanoylphorbol Acetate
  • Calcium