The effect of products of the oxidative burst on the function of neutrophil FcgammaR was studied. We have reported that inhibitors of the oxidative burst, i.e., sodium azide and catalase, enhanced PMN FcgammaR- mediated phagocytosis of SRBC coated with IgG (E-IgG). Recent studies showed that taurine and methionine (inhibitors of the late-forming oxidant,HOCl and its derivatives) also enhanced phagocytosis. E-lgG resetting and the membrane expression of 2 different Fcgamma's (FcgammaRII and FcgammaRIII) were also enhanced by the inhibitors, which in striking contrast, had not effect on the expression or function of the C3b receptor (CR1). This suggested that late-forming products of the oxidative burst down-regulate FcgammaR but not CR1. Incubation of PMN in HOCl resulted in about 50% loss in e-lgG resetting and a similar reduction in binding of 125l- mAb's against FcgammaRII, FcgammaRIII, CR3 (iC3b receptor), and beta2 microglobulin (beta2m), but not that anti-HLe-1, or anti-CD67, which recognize unrelated PMN membrane antigens. CR1-mediated resetting and membrane expression were not altered by HOCl. Further incubation of immobilized PMN extracts with HOCl resulted in a significantly greater reduction in anti-FcgammaIII binding in comparison with anti-CR1 binding. Thus, HOCl or its derivatives alter PMN FcgammaR's such that they are no longer recognized by their specific ligand, lgG resulting in the modulation of the function of these important opsonic receptors. It was shown, however, that after incubation for 30 min at 30 degrees celsius, that was significant recovery in binding of anti-FcgammaRIII to HOCl- oxidized PMN, and that exposure of HOCl- treated PMN to the reducing agent, cysteine, resulted in significant recovery of FcgammaR antigenic and functional properties. The ability of PMN to down-regulate and up- regulate receptor function may be of importance in their activity at inflammatory sites.
