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J. Exp. Med.,
Volume 188, Number 3, August 3, 1998 421-429
By
From the * Department of Internal Medicine, Interleukin (IL)-5 has been shown to activate many signaling molecules in eosinophils, but
their functional relevance remains unknown. We have examined the functional relevance of
Lyn, Jak2, and Raf-1 kinases in eosinophil survival, upregulation of adhesion molecules and
degranulation. To this goal we used Lyn and Raf-1 antisense (AS) oligodeoxynucleotides
(ODN) to inhibit the expression of these proteins and tyrphostin AG490 to specifically block
the activation of Jak2. We have demonstrated that all three kinases are important for IL-5-
induced suppression of eosinophil apoptosis. However, Lyn and Jak2 tyrosine kinases are not
important for the upregulation of CD11b and the secretion of eosinophil cationic protein. In
contrast, Raf-1 kinase is critical for both these functions. This is the first identification of specific
signaling molecules responsible for three important functions of eosinophils. We have established a central role for Raf-1 kinase in regulating eosinophil survival, expression of
Department
of Pediatrics, The University of Texas Medical Branch, Galveston, Texas 77555-0762
2 integrins
and degranulation. Further, there appears to be a dissociation between two receptor-associated tyrosine kinases, i.e., Lyn and Jak2, and the activation of Raf-1 kinase. The delineation of the
functional relevance of signaling molecules will help design therapeutic approaches targeting
specific eosinophil function.
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