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Blood, Vol. 92 No. 3 (August 1), 1998:
pp. 778-783
RAPID COMMUNICATION
Role for Bcl-xL in Delayed Eosinophil Apoptosis
Mediated by Granulocyte-Macrophage Colony-Stimulating Factor and
Interleukin-5
Birgit Dibbert,
Isabelle Daigle,
Doris Braun,
Corinna Schranz,
Martina Weber,
Kurt Blaser,
Uwe Zangemeister-Wittke,
Arne N. Akbar, and
Hans-Uwe Simon
From the Swiss Institute of Allergy and Asthma Research (SIAF),
University of Zurich, Davos, Switzerland; Clinic for Dermatology and
Allergy, Davos, Switzerland; the Department of Internal Medicine, the
Division of Oncology, University Hospital, Zurich, Switzerland; and the
Department of Clinical Immunology, The Royal Free Hospital School of
Medicine, London, UK.
Eosinophils are potent inflammatory cells involved in allergic
reactions. Inhibition of apoptosis of purified eosinophils by certain
cytokines has been previously shown to be an important mechanism
causing tissue eosinophilia. To elucidate the role of Bcl-2 family
members in the inhibition of eosinophil apoptosis, we examined the
expression of the known anti-apoptotic genes Bcl-2, Bcl-xL,
and A1, as well as Bax and Bcl-xS, which promote apoptosis in other systems. We show herein that freshly isolated human
eosinophils express significant amounts of Bcl-xL and Bax,
but only little or no Bcl-2, Bcl-xS, or A1. As assessed by
reverse transcription-polymerase chain reaction, immunoblotting, flow
cytometry, and immunocytochemistry, we show that spontaneous eosinophil
apoptosis is associated with a decrease in Bcl-xL mRNA and
protein levels. In contrast, stimulation of the cells with
granulocyte-macrophage colony-stimulating factor (GM-CSF) or
interleukin-5 (IL-5) results in maintenance or upregulation of
Bcl-xL mRNA and protein levels. Moreover, Bcl-2 protein is not induced by GM-CSF or IL-5 in purified eosinophils. Bcl-2 protein is
also not expressed in tissue eosinophils as assessed by
immunohistochemistry using two different eosinophilic tissue models.
Furthermore, Bcl-xL antisense but not scrambled
phosphorothioate oligodeoxynucleotides can partially block the
cytokine-mediated rescue of apoptotic death in these cells. These data
suggest that Bcl-xL acts as an anti-apoptotic molecule in
eosinophils.
© 1998 by The American Society of Hematology.
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