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

Natalia Vilariño, Donald W. MacGlashan

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)928-937
Number of pages10
JournalJournal of Leukocyte Biology
Volume75
Issue number5
DOIs
StatePublished - May 2004

Keywords

  • Antigen
  • Erk
  • Latrunculin
  • Syk

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Fingerprint Dive into the research topics of 'Actin cytoskeleton-dependent down-regulation of early IgE-mediated signaling in human basophils'. Together they form a unique fingerprint.

Cite this