Abstract

Murine granulocytes and precursors express low-affinity IgG Fc receptors (Fc gammaR). We investigated the effects of FcyR ligation on the development of eosinophils in cultures of normal murine bone marrow. Eosinophilopoiesis was induced by culture of bone marrow cells in the presence of cytokines (granulocyte-macrophage colony-stimulating factor [GM-CSF], interleukin-3 [IL-3], and IL-5). Addition to the cultures of 2.4G2, a rat monoclonal antibody (mAb) that reacts with Fc gammaRII (CD32) and Fc gammaRIII (CD16), induced granulocyte apoptosis within 24 hours. Granulocytes in cultures that contained 2.4G2 showed chromatin condensation, binding of Annexin-V, and fas induction, and by electron microscopy, apoptosis was most commonly observed in cells of the eosinophil lineage. Since murine granulocytes can express both Fc gammaRII (CD32) and Fc gammaRIII (CD16), we investigated the effect of 2.4G2 on cultures of bone marrow obtained from Fc gammaRIII (CD16) gene-disrupted mice and found that the apoptosis induced with 2.4G2 was CD16-independent. Studies with bone marrow cultures from B6MLR-lpr/lpr and C3H/HEJ-gld/gld mice established that the Fc gammaRII (CD32)-triggered apoptosis was fas-fasL-dependent. When mature eosinophils isolated from hepatic granulomas of Schistosoma mansoni-infected mice were cultured in cytokines in the presence of 2.4G2, the eosinophils underwent apoptosis within 24 hours. These findings identify a previously unknown linkage between Fc gammaR on eosinophils and fas-mediated apoptosis, a connection that could be relevant to mechanisms by which eosinophils mediate tissue injury and antibody-dependent cellular cytotoxicity reactions.