Ligation of Fc gamma RII (CD32) pivotally regulates survival of human eosinophils

The low-affinity IgG Fc receptor, Fc gamma RII (CD32), mediates various eff ector functions of lymphoid and myeloid cells and is the major IgG Fc recep tor expressed by human eosinophils. We investigated whether Fc gamma RII re gulates both cell survival and death of human eosinophils. When cultured in vitro without growth factors, most eosinophils undergo apoptosis within 96 h, Ligation of Fc gamma RII by anti-CD32 mAb in solution inhibited eosinop hil apoptosis and prolonged survival in the absence of growth factors. Cros s-linking of human IgG bound to Fc gamma RII by anti-human IgG Ab or of uno ccupied Fc gamma RII by aggregated human IgG also prolonged eosinophil surv ival. The enhanced survival with anti-CD32 mAb was inhibited by anti-granul ocyte-macrophage-CSF (GM-CSF) mAb, suggesting that autocrine production of GM-CSF by eosinophils mediated survival. In fact, mRNA for GM-CSF was detec ted in eosinophils cultured with anti-CD32 mAb, In contrast to mAb or ligan ds in solution, anti-CD32 mAb or human IgG, when immobilized onto tissue cu lture plates, facilitated eosinophil cell death even in the presence of IL- 5. Cell death induced by these immobilized ligands was accompanied by DNA f ragmentation and was inhibited when eosinophil beta(2) integrin was blocked by anti-CD18 mAb, suggesting that beta(2) integrins play a key role in ini tiating eosinophil apoptosis, Thus, Fc gamma RII may pivotally regulate bot h survival and death of eosinophils, depending on the manner of receptor li gation and beta(2) integrin involvement. Moreover, the Fc gamma RII could p rovide a novel mechanism to control the number of eosinophils at inflammati on sites in human diseases.