Van Winkle L S, Buckpitt A R, Nishio S J, Isaac J M, Plopper C G
Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis 95616-8732, USA.
Am J Physiol. 1995 Dec;269(6 Pt 1):L800-18. doi: 10.1152/ajplung.1995.269.6.L800.
Clara cells, progenitors for bronchiolar epithelium, are also primary targets for metabolically activated pulmonary cytotoxicants and have an abundance of the cytochrome P-450 monooxygenases required for xenobiotic metabolism. To define the repair pattern after massive Clara cell injury, mice were treated with naphthalene, and lungs evaluated 1-14 days postinjury (DPI). Clara cells of terminal bronchioles were vacuolated and swollen 1 DPI, exfoliated 2 DPI, and resembled controls at 14 DPI. The volume fraction of vacuolated cells was highest 1 and 2 DPI and minimal at 5-7 DPI. The volume fraction of normal nonciliated cells decreased 40% at 1 DPI. Cell proliferation increased within epithelium and interstitium at 1 DPI, was maximal at 2 DPI, and at all other time points was similar to baseline levels. Expression of Clara cell differentiation markers was barely detectable in terminal bronchiolar epithelium at 1 and 2 DPI, clearly detectable at 4 DPI, and gradually returned to control levels at 5-14 DPI. We conclude that bronchiolar epithelial repair after naphthalene injury involves distinct phases of proliferation and differentiation, proliferation of cells that are not differentiated Clara cells, and interaction of multiple cell types including nontarget cells.
细支气管上皮祖细胞克拉拉细胞也是代谢活化的肺细胞毒性物质的主要靶细胞，并且具有外源性物质代谢所需的丰富的细胞色素P - 450单加氧酶。为了确定大量克拉拉细胞损伤后的修复模式，用萘处理小鼠，并在损伤后1 - 14天（DPI）评估肺组织。终末细支气管的克拉拉细胞在损伤后1天出现空泡化和肿胀，2天脱落，14天时与对照相似。空泡化细胞的体积分数在1天和2天时最高，在5 - 7天时最低。正常无纤毛细胞的体积分数在1天时下降了40%。细胞增殖在1天时上皮和间质内增加，在2天时达到最大，在所有其他时间点与基线水平相似。克拉拉细胞分化标志物的表达在1天和2天时在终末细支气管上皮中几乎检测不到，在4天时可清楚检测到，并在5 - 14天时逐渐恢复到对照水平。我们得出结论，萘损伤后细支气管上皮修复涉及增殖和分化的不同阶段、未分化的克拉拉细胞的增殖以及包括非靶细胞在内的多种细胞类型的相互作用。
