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

Inflammatory-cell infiltration and epithelial modifications are prominent l esions of the bronchial mucosa in asthma and in experimental allergic bronc hopulmonary inflammation. However, the recruitment of inflammatory cells an d their relationship to the epithelial modifications and to functional alte rations such as bronchopulmonary hyperreactivity (BHR) are less known. We s tudied the mechanisms of antigen-dependent inflammatory-cell recruitment to the lungs and the associated lesions and their relationship using drug- an d antibody-dependent cell-depletion procedures. A single intranasal ovalbum in challenge in BP2 mice was found to induce hyperreactivity within 1 h aft er challenge, followed by the massive infiltration of immunoglobulin (Ig)E- bearing polymorphonuclear leukocytes (PMN), and eosinophils, and by a mucou s-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-cel l metaplasia, and BHR were prevented by prior antibody-dependent depletion of CD3(+) lymphocytes and partially inhibited by the depletion of CD4(+) ly mphocytes. Treatment with the granulocytopenic drug vinblastine before chal lenge completely abolished the recruitment of granulocytes without affectin g the antigen-induced mucous-cell metaplasia. Tn this study two new key ele ments 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.