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Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224
Previous studies have indicated a redundancy in the effects of the
cytokines, IL-3, IL-5, and nerve growth factor (NGF) on acute priming
of human basophils. In the current study, we have examined the effects
of these three cytokines on 18-h priming for leukotriene C4
generation, their ability to induce Fc
RI
mRNA expression, or
their ability to sustain basophil viability in culture. We also examine
a variety of the signaling steps that accompany activation with these
cytokines. In contrast with the ability of IL-3 to alter
secretagogue-mediated cytosolic calcium responses following 18-h
cultures, 18-h treatment with IL-5 or NGF did not affect C5a-induced
leukotriene C4 generation or alter C5a-induced intracellular
Ca2+ concentration elevations. IL-3 and IL-5, but
not NGF, induced Fc
RI
mRNA expression and all three improved
basophil viability in culture with a ranking of IL-3 > IL-5
NGF. All three cytokines acutely activated the extracellular
signal-regulated kinase pathway and the signaling elements that
preceded extracellular signal-regulated kinase and cytosolic
phospholipase A2 phosphorylation, consistent with their
redundant ability to acutely prime basophils. However, only IL-3 and
IL-5 induced Janus kinase 2 and STAT5 phosphorylation. This pattern of
signal element activation among the three cytokines most closely
matched their ability to induce expression of Fc
RI
mRNA.
Induction of the sustained calcium signaling that follows overnight
priming with IL-3 appeared to be related to the strength of the early
signals activated by these cytokines but the relevant pathway required
was not identified. None of the signaling patterns matched the ability
of the cytokines to promote basophil survival.
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