Anti-FcγR IgM monoclonal antibodies (mAbs) isolated from lipopolysaccharide-stimulated spleen cells from tightskin (TSK) mice were found to be polyspecific, reacting with a wide variety of molecules, including double-stranded DNA, topoisomerase, RNA polymerase, and different collagen types. Approximately 60% of the polyspecific IgM mAbs have anti-FcγR specificity. These anti-FcγR mAbs induce the release of hydrolases from both azurophil and specific granules of human neutrophils. 25-45% of the total cellular content (determined in Nonidet P-40 lysates) of neutrophil elastase, 10-25% of β-glucuronidase, and 30-50% of alkaline phosphatase was released after incubation with the mAbs. The degranulation process was accompanied by dramatic morphological changes shown by scanning and transmission electron microscopy. The release of hydrolytic enzymes stimulated by the IgM anti-FcγR mAbs was inhibited by preincubation of neutrophils with Fab fragments of either anti-human FcγRII (IV.3) or anti-human FcγRIII (3G8) mAbs. The binding of the anti-FcγR TSK mAbs to human neutrophils was inhibited by Fab fragments of mAb 3G8. However, we found that the TSK anti-Fc-yR mAbs do not bind to human FcγRII expressed in either CHO cells or the P388D1 mouse macrophage cell line. Since the enzyme release could be inhibited by Fab fragments of mAb IV.3, we suggest that the signal transduction may require FcγRII activation subsequent to crosslinking of the glycan phosphatidyl inositol-anchored FcγRIII-1. These data demonstrate for the first time that polyspecific autoantibodies with FcγR specificity can trigger neutrophil enzyme release via human FcγRIII-1 in vitro and indicate a possible role for such autoantibodies in autoimmune inflammatory processes.

Original languageEnglish
Pages (from-to)1473-1482
Number of pages10
JournalJournal of Experimental Medicine
Issue number6
StatePublished - 1 Jun 1991


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