Calcium signalling is altered in myeloid cells with a deficiency in NADPH oxidase activity.
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.
Rada
B K
BK
Department of Physiology, Semmelweis University, Budapest, Hungary.
Geiszt
M
M
Van Bruggen
R
R
Nemet
K
K
Roos
D
D
Ligeti
E
E
D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002460:Cell Line; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006105:Granulomatous Disease, Chronic / Q000378:metabolism*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute; D008345:Manganese / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D022423:Myeloid Cells / Q000378:metabolism*; D019255:NADPH Oxidases / Q000172:deficiency*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009861:Onium Compounds / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004791:Enzyme Inhibitors; D009861:Onium Compounds; D013481:Superoxides; D008345:Manganese; C007517:diphenyleneiodonium; D019001:Nitric Oxide Synthase; D019255:NADPH Oxidases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium