Characterization of FcalphaR-triggered Ca(2+) signals: role in neutrophil NADPH oxidase activation.
Human neutrophil IgA receptors (FcalphaR) trigger phagocytosis of IgA-opsonized particles and activate the NADPH oxidase complex ultimately leading to pathogen destruction. Signal transduction events triggered by FcalphaR have not been investigated in the context of NADPH oxidase activation. In this study, we show that crosslinking FcalphaR triggers the release of Ca(2+) from an intracellular store that was unchanged by the addition of extracellular EGTA. This was in contrast to the thapsigargin-triggered Ca(2+) signal, which activates store-operated Ca(2+) entry pathways (SOCP) and is sensitive to extracellular EGTA. Buffering extracellular Ca(2+) with EGTA had no effect on FcalphaR-triggered NADPH oxidase activation, suggesting that SOCP was not required for activation by FcalphaR. EGTA inhibited thapsigargin-triggered NADPH oxidase activation but had no effect on PMA-triggered responses. The intracellular Ca(2+) chelator BAPTA caused dose-dependent inhibition of both FcalphaR-triggered and thapsigargin-triggered NADPH oxidase activation but had no effect on PMA-triggered responses. Our data demonstrate that FcalphaR-triggered NADPH oxidase activation is dependent on the release of Ca(2+) from an intracellular store, but is independent of SOCP.
Lang
M L
ML
Department of Molecular and Cellular Pathology, Ninewells Hospital and Medical School, Dundee, DD1 9SY, Scotland. M.L.Lang@Dartmouth.edu
Kerr
M A
MA
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology* / Q000378:metabolism; D011961:Receptors, Fc / Q000502:physiology*; D019284:Thapsigargin / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D004791:Enzyme Inhibitors; C036832:Fc(alpha) receptor; D011961:Receptors, Fc; D019284:Thapsigargin; D019255:NADPH Oxidases; D002118:Calcium