Mast cell desensitization inhibits calcium flux and aberrantly remodels actin.
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.
W X Gladys
WX
Ang
Alison M
AM
Church
Mike
M
Kulis
Hae Woong
HW
Choi
A Wesley
AW
Burks
Soman N
SN
Abraham
D008841:Actin Cytoskeleton / Q000276:immunology*; D000199:Actins / Q000276:immunology; D000707:Anaphylaxis / Q000276:immunology* / Q000473:pathology; D000818:Animals; D016466:CHO Cells; D020013:Calcium Signaling / Q000276:immunology*; D015550:Cell Degranulation / Q000276:immunology*; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D007073:Immunoglobulin E / Q000276:immunology; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology; D051379:Mice; D017455:Receptors, IgE / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*
D000199:Actins; D017455:Receptors, IgE; D007073:Immunoglobulin E
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