Increased susceptibility of 129SvEvBrd mice to IgE-Mast cell mediated anaphylaxis

<p>Abstract</p> <p>Background</p> <p>Experimental analyses have identified strain-dependent factors that regulate susceptibility to anaphylaxis in mice. We assessed the susceptibility of the widely used 129SvEvBrd (also known as 129S5) mouse strain to IgE/mast cell-mediated anaphylaxis as compared to BALB/c. Mice were subjected to passive and oral Ovalbumin [OVA]-induced active anaphylaxis. Tissue mast cell, plasma histamine, total IgE and OVA-specific IgE levels and susceptibility to histamine i.v infusion were assessed. Bone marrow mast cell (BMMC)s were examined for Fc_εRI, c-kit, degranulation efficiency, proliferation, apoptosis and cytokine profile.</p> <p>Results</p> <p>129S5 mice had significantly increased susceptibility to passive and oral OVA-induced active anaphylaxis. Increased susceptibility to anaphylaxis was associated with increased homeostatic mast cell levels but not OVA-specific IgE or IgG₁levels. <it>In vitro </it>analyses of BMMCs revealed no difference in Fc_εRI and c-Kit expression, however, 129S5 BMMCs possessed greater proliferative capacity and reduced caspase-3-mediated apoptosis. IgE-BMMC degranulation assays demonstrated no difference in degranulation efficiency. Furthermore, 129S5 mice possessed increased sensitivity to histamine-induced hypothermia.</p> <p>Conclusions</p> <p>We conclude that 129S5 mice have increased susceptibility to anaphylaxis as compared to BALB/c strain and their increased susceptibility was associated with altered mast cell proliferation and homeostatic tissue levels and responsiveness to histamine. Given the wide spread usage of the 129SvEvBrd strain of mice in experimental gene targeting methodology, these data have important implications for studying IgE-reactions in mouse systems.</p

Differential roles for the IL-9/IL-9 receptor alpha-chain pathway in systemic and oral antigen-induced anaphylaxis.

The cytokine IL-9 has been implicated in allergic reactions, including food allergy, but its contribution to parenteral versus oral antigen-induced anaphylaxis remains unclear

Mast cells regulate homeostatic intestinal epithelial migration and barrier function by a chymase/Mcpt4-dependent mechanism

Altered intestinal barrier function is postulated to be a central predisposing factor to intestinal diseases, including inflammatory bowel diseases and food allergies. However, the mechanisms involved in maintaining homeostatic intestinal barrier integrity remain undefined. In this study, we demonstrate that mice deficient in mast cells (KitW-sh/W-sh [Wsh]) or mast cell chymase (Mcpt4−/−) have significantly decreased basal small intestinal permeability compared with wild-type (WT) mice. Altered intestinal barrier function was linked to decreased intestinal epithelial cell migration along the villus/crypt axis, altered intestinal morphology, and dysregulated claudin-3 crypt expression. Remarkably, engraftment of Wsh mice with WT but not Mcpt4−/− mast cells restored intestinal epithelial cell migration, morphology, and intestinal epithelial barrier function. Collectively, these findings identify a mechanism by which mast cells regulate homeostatic intestinal epithelial migration and barrier function