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

Journal of Leukocyte Biology

Donald W. MacGlashan Jr¹  Natalia Vilariño¹ 

[1] Johns Hopkins Asthma and Allergy Center, Baltimore, MarylandJohns Hopkins Asthma and Allergy Center, Baltimore, MarylandJohns Hopkins Asthma and Allergy Center, Baltimore, Maryland

关键词: antigen;    latrunculin;    syk;    Erk;   

DOI  :  10.1189/jlb.0903431

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Two regions of down-regulation of FcεRI [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 FcεRI 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 FcεRI 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.

【 授权许可】

Unknown