Regulation of capacitative Ca2+ influx in human neutrophil granulocytes. Alterations in chronic granulomatous disease.
Ca2+ entry through the capacitative (store-regulated) pathway was shown to be inhibited in neutrophil granulocytes by the protein kinase C activator phorbol 12-myristate 13-acetate and the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (fMLP) by a hitherto unknown mechanism. Measuring both Ca2+ and Mn2+ entry into store-depleted cells we show in the present study that inhibition of the capacitative pathway is absent in various forms of chronic granulomatous disease. To establish the possible relationship between inhibition of the capacitative pathway and ability of O-2 production and consequent membrane depolarization, gradual changes of the membrane potential were evoked in neutrophils of healthy individuals. This was accomplished by pharmacological manipulation of the membrane potential and by variations of the concentration and type of the stimulant. Close relationship was observed between membrane depolarization and inhibition of Mn2+ entry through the capacitative transport route. Our results provide an explanation for the inhibitory action of fMLP and phorbol 12-myristate 13-acetate on capacitative cation influx and reveal that upon physiological stimulation, Ca2+ entry into neutrophils is restricted by the depolarization accompanying O-2 production.
Geiszt
M
M
Department of Physiology and Laboratory of Cellular and Molecular Physiology, Semmelweis Medical University, H-1444 Budapest, Hungary.
Kapus
A
A
Német
K
K
Farkas
L
L
Ligeti
E
E
D002118:Calcium / Q000378:metabolism*; D006105:Granulomatous Disease, Chronic / Q000097:blood*; D006801:Humans; D017136:Ion Transport; D008345:Manganese / Q000378:metabolism; D008564:Membrane Potentials; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D013481:Superoxides / Q000097:blood; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D013481:Superoxides; D008345:Manganese; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium