Smiley-Jewell S M, Nishio S J, Weir A J, Plopper C G
Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis 95616-8732, USA.
Am J Physiol. 1998 Apr;274(4):L485-98. doi: 10.1152/ajplung.1998.274.4.L485.
Nonciliated bronchiolar (Clara) cells metabolize environmental toxicants, are progenitor cells during development, and differentiate postnatally. Because differentiating Clara cells of neonatal rabbits are injured at lower doses by the cytochrome P-450-activated cytotoxicant 4-ipomeanol than are those of adults, the impact of early injury on the bronchiolar epithelial organization of adults was defined by treating neonates (3-21 days) and examining them at 4-6 wk. Bronchiolar epithelium of 6-wk-old animals treated on day 7 was most altered from that of control animals. Almost 100% of the bronchioles were lined by zones of squamous epithelial cells. Compared with control animals, the distal bronchiolar epithelium of 4-ipomeanol-treated animals had more squamous cells (70-90 vs. 0%) with a reduced overall epithelial thickness (25% of control value), fewer ciliated cells (0 vs. 10-20%), a reduced expression of Clara cell markers of differentiation (cytochrome P-4502B, NADPH reductase, and 10-kDa protein), and undifferentiated nonciliated cuboidal cell ultrastructure. We conclude that early injury to differentiating rabbit Clara cells by a cytochrome P-450-mediated toxicant inhibits bronchiolar epithelial differentiation and greatly affects repair.
无纤毛细支气管（克拉拉）细胞可代谢环境毒物，在发育过程中是祖细胞，并在出生后分化。由于新生兔正在分化的克拉拉细胞比成年兔的细胞更容易受到细胞色素P - 450激活的细胞毒性物质4 - 异戊烯醇的低剂量损伤，因此通过对新生兔（3 - 21天）进行处理并在4 - 6周时对其进行检查，确定了早期损伤对成年兔细支气管上皮组织的影响。在第7天接受处理的6周龄动物的细支气管上皮与对照动物相比变化最大。几乎100%的细支气管内衬有鳞状上皮细胞区。与对照动物相比，用4 - 异戊烯醇处理的动物的远端细支气管上皮有更多的鳞状细胞（70 - 90%对0%），上皮总厚度降低（为对照值的25%），纤毛细胞减少（0对10 - 20%），克拉拉细胞分化标志物（细胞色素P - 4502B、NADPH还原酶和10 kDa蛋白）的表达降低，以及未分化的无纤毛立方体细胞超微结构。我们得出结论，细胞色素P - 450介导的毒物对正在分化的兔克拉拉细胞的早期损伤会抑制细支气管上皮分化并极大地影响修复。
