First Author | Ito R | Year | 2020 |
Journal | Int Immunol | PubMed ID | 33027513 |
Mgi Jnum | J:301357 | Mgi Id | MGI:6501903 |
Doi | 10.1093/intimm/dxaa067 | Citation | Ito R, et al. (2020) Bovine beta-lactoglobulin-induced passive systemic anaphylaxis model using humanized NOG hIL-3/hGM-CSF transgenic mice. Int Immunol |
abstractText | Food allergy is a common disease caused by the intake of allergen-containing foods, such as milk, eggs, peanuts, and wheat. Systemic anaphylaxis is a severe hypersensitive allergic reaction resulting from degranulation of mast cells or basophils after crosslinking of surface high affinity IgE receptors (Fcepsilon-RI) with allergen-specific IgE and allergens. In this study, we developed a novel human mast cell/basophil-engrafted mouse model that recapitulates systemic anaphylaxis triggered by beta-lactoglobulin (BLG), the major allergen found in milk. Human CD34 + hematopoietic stem cells were transferred into NOG (non-Tg) or NOG hIL-3/hGM-CSF transgenic (Tg) mice. After 14-16 weeks, bovine BLG-specific human IgE was intravenously injected into the humanized mice, followed by intravenous or oral bovine BLG exposure 1 day later. Body temperature in Tg, but not in non-Tg, mice gradually decreased within 10 minutes, and 80% of Tg mice died within 1 hour by intravenous BLG exposure. Serum histamine levels and anaphylaxis scores in Tg mice were markedly increased compared to non-Tg mice. Furthermore, these allergic symptoms were significantly inhibited by epinephrine treatment into the Tg mice. Therefore, the current NOG hIL-3/hGM-CSF Tg mouse model may be useful for development of novel anaphylaxis drugs for the treatment of food allergies and for safety assessment of low-allergenicity extensively hydrolyzed cow's milk whey protein-based infant formulas. |