Fc receptor-mediated desensitization of superoxide (O2-) generation response of guinea-pig macrophages and polymorphonuclear leucocytes.

Guinea-pig macrophages were pretreated with soluble immune complexes (1 hr, at 37 degrees). By this procedure, the capacity of the cells to produce superoxide anions (O2-) upon stimulation with wheatgerm agglutinin (WGA) was inhibited by as much as 80% (desensitization). However, the receptors for WGA were still available on the cell surfaces as determined by the binding of 125I-labelled WGA to both the pretreated and control cells. This inhibition of O2- generation was also observed when opsonized zymosan (Op-zymosan) was used as the stimulus for O2- generation. In contrast, the inhibition by soluble immune complexes was less than 25% of the control levels when the desensitized cells were stimulated with N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) or phorbol myristate acetate (PMA). The same procedure was also used to desensitize guinea-pig polymorphonuclear leucocytes (PMN). In this case, the O2- generation of the PMN was suppressed to 50-55% of the control level when WGA or fMLP was used as stimulus. However, the PMA-induced O2- generation was far less affected by this treatment, as was the case with the macrophages. The activity of the desensitized macrophages for O2- generation recovered gradually to a normal level 24 hr after removal of the immune complexes from the medium. These results suggest that (i) some regulatory mechanisms which suppress the activation of NADPH oxidase are accentuated by prolonged exposure of guinea-pig macrophages and PMN with soluble immune complexes; (ii) the mechanism for O2- generation mediated by WGA or Op-zymosan may be different from that for O2- generation mediated by PMA, and (iii) the mechanism for O2- generation mediated by fMLP differs between macrophages and PMN.