Degranulation in human neutrophils primes the cells for subsequent responsiveness to the chemoattractant N-formylmethionylleucylphenylalanine but does not increase the sensitivity of the NADPH-oxidase to an intracellular calcium rise.
Both the chemotactic peptide formylmethionylleucylphenylalanine (FMLP) and the calcium-specific ionophore ionomycin can activate the NADPH-oxidase in human neutrophils. However, since ionomycin and FMLP activity differ in their requirement for azide, a potent inhibitor of the hydrogen peroxide consuming enzymes catalase and myeloperoxidase, we propose that the two stimuli can activate different pools of the oxidase. Degranulation, induced in vitro by sn-1,2-dedecaoylglycerol or in vivo by an exudation process, resulted in a priming of the cells using FMLP as stimulating agent as well as in a reduced capacity to generate H2O2 in response to ionomycin. The sensitivity of the plasma membrane-bound NADPH-oxidase to an intracellular [Ca2+] rise, induced by the ionophore was, however, not changed by the degranulation. From these results we propose that FMLP activates the plasma membrane-bound oxidase, whereas the ionophore is capable of activating a granule-bound pool of the oxidase.
Dahlgren
C
C
Department of Medical Microbiology, University of Linköping, Sweden.
Follin
P
P
D000328:Adult; D001386:Azides / Q000494:pharmacology; D002118:Calcium / Q000097:blood*; D002634:Chemotaxis, Leukocyte; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000648:ultrastructure; D004075:Diglycerides / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009247:NADH, NADPH Oxidoreductases / Q000097:blood*; D019255:NADPH Oxidases; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D013481:Superoxides / Q000097:blood
D001386:Azides; D004075:Diglycerides; D013481:Superoxides; C044297:1,2-didecanoylglycerol; D015759:Ionomycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006861:Hydrogen Peroxide; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D002118:Calcium