A novel bovine beta-lactoglobulin-induced passive systemic anaphylaxis model using humanized NOG hIL-3/GM-CSF Tg mice

• Published in: The Journal of immunology (1950) Vol. 204; no. 1_Supplement; pp. 66 - 66.23
• Main Authors: Ito, Ryoji, Katano, Ikumi, Otsuka, Iyo, Takahashi, Takehi, Ito, Mamoru, Simons, Peter
• Format: Journal Article
• Language: English
• Published: 01.05.2020
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.204.Supp.66.23

Abstract Background Food allergy is a common disease that is caused by 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 their surface high affinity IgE receptors (Fce-RI) by allergen-specific IgE and allergens. In this study, we developed a novel human mast cell/basophil-engrafted mouse model that recapitulates systemic anaphylaxis by milk’s major allergen beta-lactoglobulin (BLG). Method Human CD34+ hematopoietic stem cells were transferred into NOG (nonTg) or NOG hIL-3/GM-CSF Tg mice. After 14–16 weeks, mature human basophils and mast cells increased in Tg mice, and bovine BLG specific human IgE was intravenously injected in these humanized mice, followed by either intravenous or oral bovine BLG protein exposure, 1 day later. Subsequently, allergic reactions were monitored by measuring body temperature, serum histamine level, and anaphylaxis scoring. Furthermore, the adrenaline agent, ‘epinephrine’ was used to investigate whether the allergic symptoms could be suppressed. Results After bovine BLG exposure, body temperature in Tg mice, but not in nonTg mice, gradually decreased within 10 minutes and 80 % of Tg mice died within 60 minutes. Serum histamine levels and anaphylaxis scores in Tg mice were markedly increased compared to nonTg mice after 30 minutes BLG challenge. These allergic symptoms were significantly inhibited by epinephrine treatment in Tg mice. Discussion The current hIL-3/GM-CSF Tg mouse model could possibly be used to develop novel anaphylaxis drugs in food allergy.