A new murine model of pulmonary eosinophilic hypersensitivity: Contribution to experimental asthma,☆☆,,★★

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Abstract

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. (J Allergy Clin Immunol 1997;100:383-8.)

Section snippets

Animals

F1(BALB/c x A/J), BALB/c, A/J, C57Bl/6J, and CH3/HePas mice (6 to 8 weeks of age) were obtained from our own animal facilities.

Heat-coagulated hen's egg white

Separated hen's egg white was placed in a water bath at 100° C for 30 minutes. The solidified egg white was washed in distilled water, dehydrated in 100% ethanol for 48 hours, and cut into small fragments of 4 × 2 × 2 mm, weighing about 40 mg each. The egg white fragments were rehydrated in Dulbecco's phosphate-buffered saline (PBS) for 2 hours before implantation.

Heat-aggregated ovalbumin

Cells in the BAL

Groups of F1 (BALB/c X A/J) mice were immunized with OA-AL or with EWI and 14 days later challenged intratracheally with aggregated ovalbumin. Fig. 1 shows that 48 hours after antigen challenge, the total number of cells in the BAL increased significantly in OA-AL and EWI-immunized groups in comparison with nonimmunized mice.

. Cell infiltration into BAL of mice after stimulation with antigen. Groups of mice were immunized with OA-AL or with EWI or were nonimmunized (control). After 14 days, all

Discussion

Asthma is a chronic lung disease that is increasing in industrialized countries. A prominent eosinophil infiltrate in the airway tissue is one of the characteristic features of asthma.25 Thus it is of interest to develop experimental models that mimic this disease. Although several animal models have been described in the literature,21 all of them require adjuvants in the immunization protocols, and some of them do not present a typical allergic LPR as it occurs in human beings. We have

Acknowledgements

We thank Dr. Paulo Hilario Saldiva from the Department of Pathology, School of Medicine, University of São Paulo for the careful histopathologic analysis of the lungs and many helpful discussions.

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    From the Department of Immunology, Institute of Biomedical Sciences, University of São Paulo. Sandra Facincone and Ana Lúcia Pereira de Siqueira are postgraduate students from the Department of Pathology, School of Veterinary Medicine and the Department of Immunology, respectively, of the University of São Paulo.

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    Supported by Fundaças de Ampara a Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Pesquisa (CNPq).

    Reprint requests: Sonia Jancar, BSc, PhD, Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Av. Prof. Lineu Prestes 2415, 05508-900, São Paulo, Brazil.

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