SIGNAL-TRANSDUCTION VIA FC-GAMMA-R AND MAC-1 ALPHA-CHAIN IN MONOCYTESAND POLYMORPHONUCLEAR LEUKOCYTES

Some (VIM12, Leu-15, 5A4.C5), but not all, Mac-1-specific monoclonal a ntibodies (mAb) induced a clear respiratory burst in unprimed monocyte s but not in unprimed polymorphonuclear leucocytes (PMN). We showed th at this monocyte stimulation occurred via formation of Mac-1 mAb-Fc ga mma RI or Mac-1 mAb-Fc gamma RII complexes, as human monomeric IgG1 co uld completely block the respiratory burst induced by the murine IgG2a subclass anti-Mac-1 mAb Leu-15 and the Fc gamma RII-specific mAb IV.3 inhibited respiratory burst formation by IgG1 subclass anti-Mac-1 mAb VIM12 and 5A4.C5, respectively. F(ab')(2) fragments of mAb VIM12 did not stimulate. This association between Mac-1 and Fc gamma RII may be due to a near spatial association between these molecules in monocytes , as we observed partial inhibition of FITC-labelled anti-Fc gamma RII mAb IV.3 binding after prior incubation with mAb VIM12. If monocytes were preincubated with mAb IV.3 or aggregated IgG, there was partial i nhibition of mAb VIM12 binding. The non-stimulating anti-Mac-1 mAb (JM L.H11,44, OKM1, LM2/1, Mol) did not show any significant competition w ith mAb IV.3 binding to Fc gamma RII. Both non-stimulating CD18-specif ic mAb, however, showed strong competition with mAb IV.3 binding to Fc gamma RII. On unprimed PMN, the situation was different. No Mac-1-spe cific mAb induced a respiratory burst and there was no competitive inh ibition between anti-Mac-1 mAb and antibodies binding to Fc gamma RII. In interferon-gamma (IFN-gamma)-primed PMN, however, we observed a fu nctional association between Mac-1 and Fc gamma RI as IgG2a subclass m Ab Leu-15 induced a respiratory burst which could be inhibited by mono meric human IgG1, as observed in monocytes. However, no other anti-Mac -1 mAb was able to induce a respiratory burst in IFN-gamma-primed PMN. Therefore, a similar signal transducing capability may exist between Mac-1 and Fc gamma RI on both monocytes and PMN, despite a different r elationship between Mac-1 and Fc gamma RII on these cell populations. As no Mac-1 beta-chain-specific (CD18) mAb were able to induce a respi ratory burst in monocytes, despite being able to interact with Fc gamm a R via their Fc regions, as detected by competition with mAb IV.3 for binding to Fc gamma RII, we conclude that intracellular signalling vi a Mac-1 mAb-Fc gamma RII complexes requires the alpha-chain.