Relationship between calcium release and NADPH oxidase inhibition in human neutrophils.
The aim of this study was to investigate the possible relationship between NADPH oxidase activity and changes in cytosolic Ca(2+) in response to different agonists. Treatment of neutrophils with leukotriene B4 (LTB(4)) demonstrated characteristic changes to cytoslic Ca(2+) yielding an EC(50) of 4nM. The pA(2) values for the specific LTB(4) receptor (BLT) antagonists, U-75302 and LY-255283 were 6.32 and 6.38, respectively. Similarly, neutrophils treated with N-formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP) and platelet activating factor (PAF) exhibited changes in cytoslic Ca(2+) in a dose dependant manner with pD(2) values of 9.0 and 9.9, respectively. The phorbol ester PMA prevented elevations in cytosolic Ca(2+) in response to LTB(4), FMLP and PAF with IC(50) values of 5.88, 1.44 and 5.71nM, respectively. In addition, potent NADPH oxidase inhibitors apocynin and diphenyleneiodonium (DPI) inhibited FMLP mediated cytosolic Ca(2+) release. These results demonstrate that inhibition of the NADPH oxidase suppresses cytosolic Ca(2+) release in FMLP activated human neutrophils.
Salmon
Michael D
MD
Leukocyte and Ion Channel Research Laboratory, School of Health and Biosciences, University of East London, London, UK.
Ahluwalia
Jatinder
J
D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005233:Fatty Alcohols / Q000494:pharmacology; D006018:Glycols / Q000494:pharmacology; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology
D005233:Fatty Alcohols; D006018:Glycols; D020024:Leukotriene Antagonists; D018102:Receptors, Leukotriene B4; D013777:Tetrazoles; C062137:U 75302; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019255:NADPH Oxidases; C063823:LY 255283; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium