Loss of Basal Cells Precedes Bronchiolitis Obliterans–Like…基底细胞丢失先于毛细支气管炎样.pdfVIP

Loss of Basal Cells Precedes Bronchiolitis Obliterans–Like Pathological Changes in a Murine Model of Chlorine Gas Inhalation 1 2 1,3 Emily G. O’Koren , Brigid L. M. Hogan , and Michael Dee Gunn 1Department of Immunology, 2Department of Cell Biology, and 3Department of Medicine, Duke University Medical Center, Durham, North Carolina Bronchiolitis obliterans (BO) is a major cause of chronic airway dysfunction after toxic chemical inhalation. The pathophysiology CLINICAL RELEVANCE of BO is not well understood, but epithelial cell injury has been closely associated with the development of fibrotic lesions in human This report describes a novel murine model of bronchioloitis studies and in animal models of both toxin-induced and transplant- obliterans (BO), demonstrates the mechanism by which induced BO. However, whereas almost all cases and models of BO airway fibrotic lesions arise in this model, and proposes that include epithelial injury, not all instances of epithelial injury result in the loss of epithelial progenitor cells is a critical factor in the BO, suggesting that epithelial damage per se is not the critical event development of BO. Our conclusions provide significant leading to the development of BO. Here, we describe a model of insights into the pathogenesis of BO, and may suggest chlorine-induced BO in which mice develop tracheal and large air- therapeutic strategies for this disease. way obliterative lesions within 10 days of exposure to high (350 parts per million [ppm]), but not low (200 ppm), concentrations of chlo- rine gas. Importantly, these lesions arise only under conditions and in areas in which basal cells, the resident progenitor c