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Fas-mediated apoptosis in cultured human eosinophils
A Druilhe, Z Cai, S Haile, S Chouaib and M Pretolani
Unite de Pharmacologie Cellulaire, Unite Associee Institut Pasteur, Paris,
France.
Previous studies have shown that cytokine-dependent eosinophils undergo
apoptosis, yet the mechanisms governing this phenomenon remain obscure. Fas
antigen is a transmembrane glycoprotein belonging to the tumor necrosis
factor receptor family. Cross-linking of Fas antigen in numerous cell types
leads to apoptosis. In the present study, we examined the potential role of
Fas antigen in the apoptosis of purified blood eosinophils from healthy
donors. Cytokine-deprived eosinophils exhibited a time-dependent loss in
viability, accompanied by an increase in the number of apoptotic nuclei and
in the expression of Fas antigen and its mRNA, as shown by flow cytometry
and reverse transcriptase-polymerase chain reaction, respectively.
Cross-linking of Fas antigen with an agonistic anti-Fas monoclonal antibody
(MoAb) induced a dose- and time-dependent increase in the number of
apoptotic nuclei. Furthermore, using an in vitro coculture system, we
showed engulfment of anti-Fas MoAb-treated eosinophils by monocyte-derived
macrophages. Finally, incubation of eosinophils with the corticosteroid,
dexamethasone, induced apoptosis and augmented that triggered by anti-Fas
MoAb. Together, these observations suggest that Fas antigen expression and
activation is involved in the apoptosis of human eosinophils and may
contribute to the resolution of inflammatory allergic reactions in which
eosinophil accumulation is a prominent feature.
Volume 87,
Issue 7,
pp. 2822-2830,
04/01/1996
Copyright © 1996 by The American Society of Hematology
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