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Mast cell desensitization inhibits calcium flux and aberrantly remodels actin.

Publication ,  Journal Article
Ang, WXG; Church, AM; Kulis, M; Choi, HW; Burks, AW; Abraham, SN
Published in: J Clin Invest
November 1, 2016

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.

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Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

November 1, 2016

Volume

126

Issue

11

Start / End Page

4103 / 4118

Location

United States

Related Subject Headings

  • Signal Transduction
  • Receptors, IgE
  • Mice
  • Mast Cells
  • Immunology
  • Immunoglobulin E
  • Disease Models, Animal
  • Cricetulus
  • Cricetinae
  • Cell Degranulation
 

Citation

APA
Chicago
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MLA
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Ang, W. X. G., Church, A. M., Kulis, M., Choi, H. W., Burks, A. W., & Abraham, S. N. (2016). Mast cell desensitization inhibits calcium flux and aberrantly remodels actin. J Clin Invest, 126(11), 4103–4118. https://doi.org/10.1172/JCI87492
Ang, WX Gladys, Alison M. Church, Mike Kulis, Hae Woong Choi, A Wesley Burks, and Soman N. Abraham. “Mast cell desensitization inhibits calcium flux and aberrantly remodels actin.J Clin Invest 126, no. 11 (November 1, 2016): 4103–18. https://doi.org/10.1172/JCI87492.
Ang WXG, Church AM, Kulis M, Choi HW, Burks AW, Abraham SN. Mast cell desensitization inhibits calcium flux and aberrantly remodels actin. J Clin Invest. 2016 Nov 1;126(11):4103–18.
Ang, WX Gladys, et al. “Mast cell desensitization inhibits calcium flux and aberrantly remodels actin.J Clin Invest, vol. 126, no. 11, Nov. 2016, pp. 4103–18. Pubmed, doi:10.1172/JCI87492.
Ang WXG, Church AM, Kulis M, Choi HW, Burks AW, Abraham SN. Mast cell desensitization inhibits calcium flux and aberrantly remodels actin. J Clin Invest. 2016 Nov 1;126(11):4103–4118.

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

November 1, 2016

Volume

126

Issue

11

Start / End Page

4103 / 4118

Location

United States

Related Subject Headings

  • Signal Transduction
  • Receptors, IgE
  • Mice
  • Mast Cells
  • Immunology
  • Immunoglobulin E
  • Disease Models, Animal
  • Cricetulus
  • Cricetinae
  • Cell Degranulation