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Induction of apoptosis in human eosinophils by anti-Fas antibody treatment
in vitro
K Matsumoto, RP Schleimer, H Saito, Y Iikura and BS Bochner
Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224-6801, USA.
Fas antigen (CD95) can induce apoptosis of cells such as lymphocytes and
neutrophils. To determine whether Fas antigen is involved in eosinophil
apoptosis, we examined its expression and function on eosinophils in vitro.
Purified human eosinophils expressed low but consistently detectable levels
of Fas antigen. Culture of eosinophils in up to 10 ng/mL interleukin-5
(IL-5) prolonged eosinophil survival; incorporation of 1 to 1,000 ng/mL Fas
antibody led to significant reductions in IL-5-induced eosinophil viability
after 48 to 72 hours of culture. Reductions in survival could not be
overcome by IL-5 and also occurred in the absence of exogenous IL-5.
Preactivation of eosinophils with platelet-activating factor (PAF)
significantly reduced eosinophil viability without altering the
survival-reducing effects of Fas antibody treatment. In contrast, RANTES
did not affect eosinophil viability or Fas antibody-induced reductions in
eosinophil survival. After treatment with Fas antibody, electron microscopy
of eosinophils and gel electrophoresis of DNA extracted from eosinophils
demonstrated changes consistent with apoptosis. These data demonstrate that
Fas antigen can modify eosinophil survival by inducing apoptosis through a
pathway that is, at least in part, independent of the survival- promoting
effects of IL-5.
Volume 86,
Issue 4,
pp. 1437-1443,
08/15/1995
Copyright © 1995 by The American Society of Hematology
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