B. Deandres et al., FC-GAMMA-RII (CD32) IS LINKED TO APOPTOTIC PATHWAYS IN MURINE GRANULOCYTE PRECURSORS AND MATURE EOSINOPHILS, Blood, 90(3), 1997, pp. 1267-1274
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.