BACKGROUND: We have recently described a model of hypersensitivity reaction in the mouse paw, which induces a typical late-phase reaction with a marked eosinophilic infiltrate. OBJECTIVE: In the search for a murine model of asthma, this model was adapted to the lungs and compared with other models of pulmonary hypersensitivity. METHODS: A fragment of heat-coagulated hen's egg white was implanted subcutaneously, and 14 days later, the mice were challenged intratracheally with aggregated ovalbumin. Comparison was made with a group that received subcutaneous injection of soluble ovalbumin in alumen, challenged as described above and with four additional protocols of immunization and challenge. RESULTS: Forty-eight hours after challenge, the percentage of eosinophils was higher in the egg white implant group (35%) than in the group immunized with ovalbumin in alumen (10.4%). The eosinophil peroxidase activity in lung homogenates of the first group was also significantly higher (529 ng/ml) than that of the second group (43 ng/ml). These results were reproduced in five different mouse strains. Compared with five different models of lung hypersensitivity, the egg white implant model was unique in terms of persistence of the pulmonary eosinophilia. Histopathologic analysis of the lungs of mice immunized with egg white implant showed peribronchial, perivascular, and intraepithelial eosinophil infiltration; morphologic characteristics of bronchoconstriction; and patchy epithelial shedding. At 21 days, in addition to persistence of eosinophil infiltrate, enlarged alveoli, reflecting air trapping, were observed. CONCLUSION: On the basis of the characteristics of the model described here, we propose it as a suitable murine model of asthma.
BACKGROUND: We have recently described a model of hypersensitivity reaction in the mouse paw, which induces a typical late-phase reaction with a marked eosinophilic infiltrate. OBJECTIVE: In the search for a murine model of asthma, this model was adapted to the lungs and compared with other models of pulmonary hypersensitivity. METHODS: A fragment of heat-coagulated hen's egg white was implanted subcutaneously, and 14 days later, the mice were challenged intratracheally with aggregated ovalbumin. Comparison was made with a group that received subcutaneous injection of soluble ovalbumin in alumen, challenged as described above and with four additional protocols of immunization and challenge. RESULTS: Forty-eight hours after challenge, the percentage of eosinophils was higher in the egg white implant group (35%) than in the group immunized with ovalbumin in alumen (10.4%). The eosinophil peroxidase activity in lung homogenates of the first group was also significantly higher (529 ng/ml) than that of the second group (43 ng/ml). These results were reproduced in five different mouse strains. Compared with five different models of lung hypersensitivity, the egg white implant model was unique in terms of persistence of the pulmonary eosinophilia. Histopathologic analysis of the lungs of mice immunized with egg white implant showed peribronchial, perivascular, and intraepithelial eosinophil infiltration; morphologic characteristics of bronchoconstriction; and patchy epithelial shedding. At 21 days, in addition to persistence of eosinophil infiltrate, enlarged alveoli, reflecting air trapping, were observed. CONCLUSION: On the basis of the characteristics of the model described here, we propose it as a suitable murine model of asthma.
Authors: Benjamin M Matta; Giorgio Raimondi; Brian R Rosborough; Tina L Sumpter; Angus W Thomson Journal: J Immunol Date: 2012-04-16 Impact factor: 5.422
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