Ligation of Fc gamma RII (CD32) pivotally regulates survival of human eosinophils.
The low-affinity IgG Fc receptor, FcgammaRII (CD32), mediates various effector functions of lymphoid and myeloid cells and is the major IgG Fc receptor expressed by human eosinophils. We investigated whether FcgammaRII regulates both cell survival and death of human eosinophils. When cultured in vitro without growth factors, most eosinophils undergo apoptosis within 96 h. Ligation of FcgammaRII by anti-CD32 mAb in solution inhibited eosinophil apoptosis and prolonged survival in the absence of growth factors. Cross-linking of human IgG bound to FcgammaRII by anti-human IgG Ab or of unoccupied FcgammaRII by aggregated human IgG also prolonged eosinophil survival. The enhanced survival with anti-CD32 mAb was inhibited by anti-granulocyte-macrophage-CSF (GM-CSF) mAb, suggesting that autocrine production of GM-CSF by eosinophils mediated survival. In fact, mRNA for GM-CSF was detected in eosinophils cultured with anti-CD32 mAb. In contrast to mAb or ligands in solution, anti-CD32 mAb or human IgG, when immobilized onto tissue culture plates, facilitated eosinophil cell death even in the presence of IL-5. Cell death induced by these immobilized ligands was accompanied by DNA fragmentation and was inhibited when eosinophil beta2 integrin was blocked by anti-CD18 mAb, suggesting that beta2 integrins play a key role in initiating eosinophil apoptosis. Thus, FcgammaRII may pivotally regulate both survival and death of eosinophils, depending on the manner of receptor ligation and beta2 integrin involvement. Moreover, the FcgammaRII could provide a novel mechanism to control the number of eosinophils at inflammation sites in human diseases.
Kim
J T
JT
Department of Immunology, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.
Schimming
A W
AW
Kita
H
H
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D019898:Autocrine Communication / Q000276:immunology; D018821:CD18 Antigens / Q000502:physiology; D016923:Cell Death / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology; D004804:Eosinophils / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D008024:Ligands; D017452:Receptors, IgG / Q000276:immunology* / Q000378:metabolism*; D012995:Solubility
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D016207:Cytokines; D007074:Immunoglobulin G; D008024:Ligands; D017452:Receptors, IgG