Mast cell desensitization inhibits calcium flux and aberrantly remodels actin

W. X. Gladys Ang, Alison M. Church, Mike Kulis, Hae Woong Choi, A. Wesley Burks, Soman N. Abraham

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

Rush desensitization (DS) is a widely used and effective clinical strategy for the rapid inhibition of IgE-mediated anaphylactic responses. However, the cellular targets and underlying mechanisms behind this process remain unclear. Recent studies have implicated mast cells (MCs) as the primary target cells for DS. Here, we developed a murine model of passive anaphylaxis with demonstrated MC involvement and an in vitro assay to evaluate the effect of DS on MCs. In contrast with previous reports, we determined that functional IgE remains on the cell surface of desensitized MCs following DS. Despite notable reductions in MC degranulation following DS, the high-affinity IgE receptor FcμRI was still capable of transducing signals in desensitized MCs. Additionally, we found that displacement of the actin cytoskeleton and its continued association with FcμRI impede the capacity of desensitized MCs to evoke the calcium response that is essential for MC degranulation. Together, these findings suggest that reduced degranulation responses in desensitized MCs arise from aberrant actin remodeling, providing insights that may lead to improvement of DS treatments for anaphylactic responses.

Original languageEnglish
Pages (from-to)4103-4118
Number of pages16
JournalJournal of Clinical Investigation
Volume126
Issue number11
DOIs
Publication statusPublished - 2016 Nov 1
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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