Humanized Mouse Model of Mast Cell-Mediated Passive Cutaneous Anaphylaxis and Passive Systemic Anaphylaxis

Publication date: Available online 6 April 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Paul J. Bryce, Rustom Falahati, Laurie Kenney, John Leung, Christopher Bebbington, Nenad Tomasevic, Rebecca A. Krier, Chia-Lin Hsu, Leonard D. Shultz, Dale L. Greiner, Michael A. Brehm
BackgroundMast cells are a critical component of allergic responses in humans, and animal models that allow the in vivo investigation of their contribution to allergy and evaluation of new human-specific therapeutics are urgently needed.ObjectiveWe have developed a new humanized mouse model that supports human mast cell engraftment and human IgE-dependent allergic responses.MethodsThis model is based on the NOD-scid IL2rg^nullSCF/GM-CSF/IL3 (NSG-SGM3) strain of mice engrafted with human thymus, liver and hematopoietic stem cells (termed BLT).ResultsLarge numbers of human mast cells develop in NSG-SGM3 BLT mice and populate the immune system, peritoneal cavity, and peripheral tissues. The human mast cells in NSG-SGM3 BLT mice are phenotypically similar to primary human mast cells and express CD117, tryptase, and FcεRI. These mast cells undergo degranulation in an IgE-dependent and independent manner, and can be readily cultured in vitro for additional studies. Intradermal priming of engrafted NSG-SGM3 mice with a chimeric IgE containing human constant regions resulted in development of a robust passive cutaneous anaphylaxis (PCA) response. Moreover, we describe the first report of a human mast cell antigen-dependent passive systemic anaphylaxis (PSA) response in primed mice.ConclusionsNSG-SGM3 BLT mice provide a readily available source of human mast cells for investigation of mast cell biology and a pre-clinical model of PCA and PSA that can be used to investigate the pathogenesis of human allergic responses and to test new therapeutics prior to their advancement to the clinic.

Teaser

Immune engrafted NSG-SGM3 BLT mice generate high numbers of human mast cells and exhibit robust passive cutaneous anaphylaxis (PCA) and passive systemic anaphylaxis reactions (PSA)


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