FC-GAMMA-RII (CD32) IS LINKED TO APOPTOTIC PATHWAYS IN MURINE GRANULOCYTE PRECURSORS AND MATURE EOSINOPHILS

Murine granulocytes and precursors express low-affinity IgG Fc recepto rs (Fc gamma R). We investigated the effects of Fc gamma R ligation on the development of eosinophils in cultures of normal murine bone marr ow. Eosinophilopoiesis was induced by culture of bone marrow cells in the presence of cytokines (granulocyte-macrophage colony-stimulating f actor [GMCSF], interleukin-3 [IL-3], and IL-5), Addition to the cultur es of 2.4G2, a rat monoclonal antibody (mAb) that reacts with Fc gamma RII (CD32) and Fc gamma RIII (CD16), induced granulocyte apoptosis wi thin 24 hours, Granulocytes in cultures that contained 2.4G2 showed ch romatin 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 gamma RII (CD32) and Fc gamma RIII (CD16), we investigated the effect of 2.4G2 on cultures of bone marrow obtained from Fc gamma RIII (CD16) gene-disrupted mice and found that the apoptosis induced with 2.4G2 w as CD16-independent. Studies with bone marrow cultures from B6MLR-lpr/ lpr and C3H/HEJ-gld/gld mice established that the Fc gamma RII (CD32)- triggered apoptosis was fas-fasL-dependent. When mature eosinophils is olated from hepatic granulomas of Schistosoma mansoni-infected mice we re cultured in cytokines in the presence of 2.4G2, the eosinophils und erwent apoptosis within 24 hours. These findings identify a previously unknown linkage between Fc gamma R on eosinophils and fas-mediated ap optosis, a connection that could be relevant to mechanisms by which eo sinophils mediate tissue injury and antibody-dependent cellular cytoto xicity reactions. (C) 1997 by The American Society of Hematology.