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. 1994 Apr;81(4):611–617.

Signal transduction via Fc gamma R and Mac-1 alpha-chain in monocytes and polymorphonuclear leucocytes.

S J Gadd 1, R Eher 1, O Majdic 1, W Knapp 1
PMCID: PMC1422385  PMID: 8039812

Abstract

Some (VIM12, Leu-15, 5A4.C5), but not all, Mac-1-specific monoclonal antibodies (mAb) induced a clear respiratory burst in unprimed monocytes but not in unprimed polymorphonuclear leucocytes (PMN). We showed that this monocyte stimulation occurred via formation of Mac-1 mAb-Fc gamma RI or Mac-1 mAb-Fc gamma RII complexes, as human monomeric IgG1 could 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 inhibition of mAb VIM12 binding. The non-stimulating anti-Mac-1 mAb (JML.H11,44, OKM1, LM2/1, Mo1) did not show any significant competition with mAb IV.3 binding to Fc gamma RII. Both non-stimulating CD18-specific mAb, however, showed strong competition with mAb IV.3 binding to Fc gamma RII. On unprimed PMN, the situation was different. No Mac-1-specific mAb induced a respiratory burst and there was no competitive inhibition between anti-Mac-1 mAb and antibodies binding to Fc gamma RII. In interferon-gamma (IFN-gamma)-primed PMN, however, we observed a functional association between Mac-1 and Fc gamma RI as IgG2a subclass mAb Leu-15 induced a respiratory burst which could be inhibited by monomeric 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 relationship 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 respiratory burst in monocytes, despite being able to interact with Fc gamma R via their Fc regions, as detected by competition with mAb IV.3 for binding to Fc gamma RII, we conclude that intracellular signalling via Mac-1 mAb-Fc gamma RII complexes requires the alpha-chain.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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