Mast cell desensitization inhibits calcium flux and aberrantly remodels actin.

Journal Article (Journal Article)

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 FcεRI was still capable of transducing signals in desensitized MCs. Additionally, we found that displacement of the actin cytoskeleton and its continued association with FcεRI 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.

Full Text

Duke Authors

Cited Authors

  • Ang, WXG; Church, AM; Kulis, M; Choi, HW; Burks, AW; Abraham, SN

Published Date

  • November 1, 2016

Published In

Volume / Issue

  • 126 / 11

Start / End Page

  • 4103 - 4118

PubMed ID

  • 27669462

Pubmed Central ID

  • PMC5096925

Electronic International Standard Serial Number (EISSN)

  • 1558-8238

Digital Object Identifier (DOI)

  • 10.1172/JCI87492


  • eng

Conference Location

  • United States