Stimulation of the human neutrophil superoxide anion-generating system with 1-O-hexadecyl/octadecyl-2-acetyl-sn-glyceryl-3- phosphorylcholine.
1-O-Hexadecyl/octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (AGEPC) stimulated a time- and concentration-dependent generation of superoxide anion (O-2) by human neutrophils. Maximum production of O-2 occurred 60 sec subsequent to cell contact with AGEPC. Superoxide generation was reduced significantly if cells were not preincubated with cytochalasin B prior to exposure to AGEPC (0.01 to 10 microM). A time-dependent desensitization for O-2 production was demonstrated in neutrophilis which were stimulated with AGEPC prior to contact with cytochalasin B. The rate and amount of O-2 generated by AGEPC-activated neutrophils were enhanced significantly in the presence of extra-cellular calcium. However, incubation of neutrophils with ethyleneglycol-bis(beta-amino-ethyl ether) N,N'-tetra-acetate (EGTA) in calcium-free medium had no effect on the O-2 generating system. AGEPC-induced O-2 production was suppressed by the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) and the sulfhydryl reagents N-ethylmaleimide (NEM) and iodoacetic acid (1A). Sodium cyanide was inactive. Pretreatment of neutrophils with AGEPC reduced cell responsiveness to subsequent exposure to this stimulus. Desensitization of the O-2-generating system activated with AGEPC appears to be stimulus specific for leukotriene B4 (LTB4) and N-formyl-methionyl-leucyl-phenylalanine (FMLP) in that these stimuli were capable of inducing O-2 production by cells pretreated with AGEPC. However, neutrophils pretreated with AGEPC were desensitized to zymosan-activated serum (ZAS).
D002118:Calcium / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010972:Platelet Activating Factor / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism*
D010972:Platelet Activating Factor; D013481:Superoxides; D007975:Leukotriene B4; D003571:Cytochalasin B; D004533:Egtazic Acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002118:Calcium