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Accumulation of eosinophils in the lung with concomitant tissue damage are defining histopathologic features of human asthma. Through degranulation and the release of proinflammatory proteins such as major basic protein (MBP), eosinophils may perpetuate this inflammatory response. We investigated the extent of eosinophil degranulation in a murine model of allergic pulmonary inflammation. In this paradigm, the mice develop pulmonary eosinophilia, mucus hypersecretion, tissue damage, and airway edema and hyperreactivity. To evaluate the degree of eosinophil degranulation, we used a polyclonal antibody to murine MBP (mMBP) to perform dot blot analysis of bronchoalveolar lavage (BAL) cells and fluids, and immunohistochemical fluorescent analysis of lung tissue sections. After ovalbumin antigen challenge, we were unable to detect immunoreactive mMBP in the BAL fluids from either nonsensitized or sensitized mice. However, after lysis of the recoverable BAL cells, we were able to detect mMBP by immunoblot analysis, with the levels of immunoreactive mMBP directly related to the number of recoverable eosinophils. We also examined paraffin-embedded, lung tissue sections for patterns of mMBP deposition. Whereas lung sections from allergic mice revealed prominent peribronchial eosinophilia after antigen challenge, tissue sections from nonsensitized animals rarely displayed eosinophils. Despite the presence of numerous eosinophils, no immunohistologic evidence of extracellular mMBP could be found in antigen-challenged allergic mice. Furthermore, rechallenged allergic mice displayed a significant increase in the number of recruited pulmonary eosinophils but all immunoreactive mMBP was still intracellular. We conclude that the recruited pulmonary eosinophils have not substantially degranulated. These results suggest that, in this murine model of allergic inflammation, eosinophil degranulation and release of mMBP does not contribute to the observed pulmonary inflammation and airway hyperreactivity. Stelts, D., R. W. Egan, A. Falcone, C. G. Garlisi, G. J. Gleich, W. Kreutner, T. T. Kung, D. K. Nahrebne, R. W. Chapman, and M. Minnicozzi. 1998. Eosinophils retain their granule major basic protein in a murine model of allergic pulmonary inflammation. Am. J. Respir. Cell Mol. Biol. 18:463-470.
Abbreviations: bronchoalveolar lavage, BAL: fluorescein isothiocyanate, FITC: interleukin-5, IL-S; major basic protein, MBP; mouse major basic protein, mMBP: chicken egg albumin. OA; phosphate-buffered saline, PBS; rabbit anti-mouse major basic protein, rb oe-mMBP; Tris-buffered saline. TBS; Tween 20), Tw20.
Pulmonary eosinophilia is one of the distinguishing features of asthma (1, 2). Appropriate activation...