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Originally published online as doi:10.1189/jlb.0903431 on March 2, 2004

Published online before print March 2, 2004
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(Journal of Leukocyte Biology. 2004;75:928-937.)
© 2004 by Society for Leukocyte Biology

Actin cytoskeleton-dependent down-regulation of early IgE-mediated signaling in human basophils

Natalia Vilariño and Donald W. MacGlashan, Jr1

Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland

1 Correspondence: Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224. E-mail: dmacglas{at}jhmi.edu

Two regions of down-regulation of Fc{varepsilon}RI [high-affinity immunogloublin E (IgE) receptor] signaling have been localized recently in basophils. An early down-regulatory step is located proximal to syk and appears responsible for a transient syk phosphorylation in antigen-stimulated basophils. A second, more distal region appears responsible for the transient activation of the ras–extracellular-regulated kinase (Erk) pathway when syk phosphorylation is sustained in anti-IgE-stimulated basophils. As the actin cytoskeleton has been demonstrated to inhibit the early Fc{varepsilon}RI signaling in rat basophilic leukemia cells, we explored the hypothesis that the actin cytoskeleton was responsible for the transience of syk phosphorylation in antigen-stimulated basophils. The inhibition of F-actin polymerization with latrunculin A induced a sustained syk phosphorylation in basophils stimulated with an optimal dose of the antigen benzyl penicilloyl–human serum albumin. However, in the presence of latrunculin A, Erk phosphorylation remained transient after stimulation with the antigen or anti-IgE. Latrunculin A also increased downstream events such as histamine release, leukotriene C4 release, and the intracellular calcium signal, although some of these effects were not specific for an immunologic stimulus. Our results suggest that the actin cytoskeleton is responsible for down-regulation of Fc{varepsilon}RI signaling at a point located proximal to syk phosphorylation. Moreover, the fact that latrunculin A did not result in sustained Erk phosphorylation supports the presence of a second down-regulatory step between syk and Erk that cannot be overcome by a sustained early signal.

Key Words: antigen • latrunculin • syk • Erk




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