Am. J. Respir. Cell Mol. Biol., Volume 20, Number 5, May, 1999 891-902

Mucous-Cell Metaplasia and Inflammatory-Cell Recruitment Are Dissociated in Allergic Mice after Antibody- and Drug-Dependent Cell Depletion in a Murine Model of Asthma

Solomon Haile, Jean Lefort, Danielle Joseph, Pierre Gounon, Michel Huerre, and B. Boris Vargaftig

Unité d'Histopathologie, Station Centrale de Microscopie Electronique, and Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur-INSERM, U485, Paris, France

Inflammatory-cell infiltration and epithelial modifications are prominent lesions of the bronchial mucosa in asthma and in experimental allergic bronchopulmonary inflammation. However, the recruitment of inflammatory cells and their relationship to the epithelial modifications and to functional alterations such as bronchopulmonary hyperreactivity (BHR) are less known. We studied the mechanisms of antigen-dependent inflammatory-cell recruitment to the lungs and the associated lesions and their relationship using drug- and antibody-dependent cell-depletion procedures. A single intranasal ovalbumin challenge in BP2 mice was found to induce hyperreactivity within 1 h after challenge, followed by the massive infiltration of immunoglobulin (Ig)E-bearing polymorphonuclear leukocytes (PMN), and eosinophils, and by a mucous-cell metaplasia of the bronchiolar epithelium. Similarly challenged BALB/c mice did not exhibit BHR, despite a moderate recruitment of inflammatory cells and mucous-cell metaplasia. Inflammatory-cell recruitment, mucous-cell metaplasia, and BHR were prevented by prior antibody-dependent depletion of CD3⁺ lymphocytes and partially inhibited by the depletion of CD4⁺ lymphocytes. Treatment with the granulocytopenic drug vinblastine before challenge completely abolished the recruitment of granulocytes without affecting the antigen-induced mucous-cell metaplasia. In this study two new key elements of the murine model of allergic pulmonary inflammation are described: the recruitment of IgE-bearing PMN between 3 and 72 h after challenge, and the dissociation between granulocytes and mucous-cell metaplasia.

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