Prevention of lung eosinophilic inflammation by oral tolerance.

Airway inflammation plays a major role in human asthma. Increasing evidence points to a close correlation between eosinophil infiltration and allergic lung disease. A new murine model of eosinophilic lung inflammation has recently been developed; it consists of immunizing mice with small fragments of solidified hen egg white implanted (EWI) into the subcutaneous tissue. In this model, which is further characterized here, mice challenged with ovalbumin (OVA) present an intense and persistent lung eosinophilia, as well as histopathological findings that resemble human asthma. In the present work, the effect of oral tolerance on the development of allergic lung inflammation in B6 mice immunized with antigen plus adjuvant or with EWI is investigated. It was found that in mice rendered orally tolerant by previous exposure to antigen in the drinking water, the T-helper type 2 cell (Th2)-associated allergic responses in both protocols of immunization were almost completely abolished. The allergic responses were assessed by pulmonary and bone marrow eosinophilia, lung histopathology and antigen-specific IgE and IgG1 production. These findings provide the first indication that Th2-associated lung pathology can be prevented by oral tolerance.

A new murine model of pulmonary eosinophilic hypersensitivity: contribution to experimental 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.

A novel murine model of late-phase reaction of immediate hypersensitivity.

We describe here a novel experimental model of late-phase reaction of immediate hypersensitivity developed in mice. It consists of introducing small fragments of heat-coagulated hen egg white into the subcutaneous tissue of mice. After 14 days, animals challenged with purified ovalbumin into the footpad presented an immediate swelling of the paw peaking at 30 min, followed by two peaks of swelling at 6 and 24 h. Histological examination of the paws showed a massive eosinophil infiltration (more than 800 cells/5 microscopic fields). This intense infiltration persisted for more than 14 days after the challenge. Furthermore, in mice immunized with coagulated egg white the delayed swelling of the paws and eosinophilic infiltration were significantly higher than in mice immunized with the classical protocol of ovalbumin in alumen adjuvant. Transfer of lymph node cells obtained from mice implanted with heat-coagulated hen egg white induced footpad swelling and eosinophil infiltration in response to ovalbumin. High levels of ovalbuminspecific IgG1 but not of IgE were detected in the serum of these animals. The advantages of this model for the experimental study of late-phase reaction per se and its relevance to the study of allergic diseases such as asthma are discussed.