Consequences of Fc gamma receptor type III reactivity in non-organ-specific autoimmune diseases

Abstract

Polymorphonuclear neutrophils (PMNs) express constitutively the Fc gamma receptors (Fc gamma Rs) Fc gamma RIIIb and Fc gamma RIIa for the Fc part of IgG, and soluble Fc gamma RIIIb (sFc gamma RIIIb) has been identified. Elevated levels of sFc gamma RIIIb were detected in non-organ-specific autoimmune conditions, and there was a considerably decreased number of PMNs undergoing apoptosis in the presence of sFc gamma RIIIb. Anti-Fc gamma RIIIb autoantibodies (autoAbs) have also been described in such patients. They are not cytotoxic to these cells, but they extend their survival. The anti-apoptotic signal can be transduced through Fc gamma RIIa and/or CD11b, the beta-chain of the complement receptor 3. However, Fc gamma RIIIb appears to be also competent. Anti-Fc gamma RIIIb-conditioned supernatant from cultured PMNs induces the transcription of messenger RNA for granulocyte colony-stimulating factor and granulocyte/macrophage colony-stimulating factor, followed by protein synthesis. The delay in apoptosis may be generated by a downregulation of the death promoter Bax. Inflammation might thus be modulated by sFc gamma RIIIb and anti-Fc gamma RIIIb autoAbs in systemic diseases.