Hydrogen peroxide activates calcium influx in human neutrophils.
The correlation between an increased production of reactive oxygen species (ROS) and an enhanced calcium entry in primed neutrophils stimulated with fMLP suggests that endogenous ROS could serve as an agonist to reinforce calcium signaling by positive feedback. This work shows that exogenous H2O2 produced a rapid influx of Mn2+ and an increase of intracellular calcium. The H2O2 was insufficient to produce significant changes in the absence of extracellular calcium but addition of Ca2+ to H2O2-treated cells suspended in a free Ca2+/EGTA buffer resulted in a great increase in [Ca2+]i reflecting influx of Ca2+ across the cell membrane. The increase of intracellular calcium was inhibited by Ni2+, La3+, and hyperosmotic solutions of mannitol and other osmolytes. This raises the possibility that the secretion of H2O2 by activated neutrophils could act as an autocrine regulator of neutrophil function through the activation of calcium entry.
Giambelluca
Miriam S
MS
Facultad de Ciencias Médicas, UNLP, Centro de Investigaciones Cardiovasculares, 60 y 120, 1900 La Plata, Argentina.
Gende
Oscar A
OA
D002021:Buffers; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D003571:Cytochalasin B / Q000494:pharmacology; D016257:Fura-2; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007811:Lanthanum / Q000494:pharmacology; D008345:Manganese / Q000378:metabolism; D008353:Mannitol / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D009532:Nickel / Q000494:pharmacology; D009995:Osmosis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012996:Solutions
D002021:Buffers; D017382:Reactive Oxygen Species; D012996:Solutions; D003571:Cytochalasin B; D008353:Mannitol; D008345:Manganese; D009240:N-Formylmethionine Leucyl-Phenylalanine; D007811:Lanthanum; D009532:Nickel; D006861:Hydrogen Peroxide; D002118:Calcium; D016257:Fura-2