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

Muthuvel Arumugam,Richard Ahrens,Leah C Kottyan,Xun Shang,Nives Zimmermann,Simon P Hogan,Heather Osterfeld,Fred D Finkelman,John A Maclennan,Yi Zheng

doi:10.1186/1471-2172-12-14

Abstract

BackgroundExperimental 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 FcεRI, c-kit, degranulation efficiency, proliferation, apoptosis and cytokine profile.Results129S5 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 IgG1 levels. In vitro analyses of BMMCs revealed no difference in FcεRI 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.ConclusionsWe 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.

Highlights

Experimental analyses have identified strain-dependent factors that regulate susceptibility to anaphylaxis in mice
We showed that susceptibility was associated with increased mast cell proliferative capacity, homeostatic tissue mast cell levels and responsiveness to histamine
Since we observed increased systemic mast cell levels in 129S5 compared to BALB/c mice, we examined Bone marrow mast cell (BMMC) proliferation rate and apoptosis

Summary

Introduction

Experimental analyses have identified strain-dependent factors that regulate susceptibility to anaphylaxis in mice. With the recent emergence of several gene knockout mice (FcЄRI, histamine decarboxylase, IL-4Ra) there has been significant focus on employment of animal models of IgE-mediated passive and active systemic and oral antigen-induced anaphylaxis in an attempt to decipher the relative contributions of inflammatory cells and cytokines to disease pathogenesis [6,8]. These analyses, while identifying important roles for specific molecules in IgE-mast cell mediated reactions, have identified strain-dependent factors that can influence mast cell responses [9]. Differences in susceptibility to food allergy in C3H/HeJ and BALB/c mice were associated with differential Th2 - Th1 responses [11]

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