Bleomycin-induced injury and metaplasia of alveolar type 2 cells. Relationship of cellular responses to drug presence in the lung.
Bleomycin-induced injury and metaplasia of alveolar type 2 cells. Relationship of cellular responses to drug presence in the lung.
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发表时间：
1979-08
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通讯作者：
I. Adamson;D. Bowden
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作者：
I. Adamson;D. Bowden
在博莱霉素诱导的肺纤维化中，肺泡内层经常观察到化生上皮细胞。这些细胞变化是由药物对分化 2 型细胞的直接作用引起的假设现在正在一项连续研究中进行检验，以将肺部中 3H 博来霉素的存在与肺泡上皮的损伤和修复模式相关联。单次静脉内剂量或多次小腹腔内剂量可诱导 1 型上皮细胞局灶性坏死，随后发生 2 型细胞再生。当这些细胞中脱氧核糖核酸 (DNA) 合成达到最大时，通过闪烁计数可在肺中显示大量 3H 博来霉素；在放射自显影照片中，药物似乎集中在上皮细胞中。随后看到许多异常的2型细胞。有些是双核的，有些则表现出核破坏。不会发生通常的 1 型细胞分化过程；相反，发现了多种上皮形式，包括胎儿样管状结构以及纤毛和鳞状化生细胞。肺上皮损伤和修复与博莱霉素在肺中的直接表现的相关性表明，2型细胞在细胞周期的分裂和分化阶段容易受到损伤，然后可能产生各种不适当的肺泡衬里细胞。
Metaplastic epithelial cells are often observed lining alveoli in bleomycin-induced pulmonary fibrosis. The hypothesis that these cellular changes are induced by the direct action of the drug on differentiating Type 2 cells is now examined in a sequential study to correlate the presence of 3H bleomycin in the lung with the pattern of injury and repair of the alveolar epithelium. A single intravenous dose or multiple small intraperitoneal doses induce focal necrosis of Type 1 epithelial cells followed by Type 2 cell regeneration. At the time of maximal deoxyribonucleic acid (DNA) synthesis in these cells, significant amounts of 3H bleomycin are demonstrable in the lung by scintillation counting; and in autoradiographs, the drug appears to concentrate in epithelial cells. Subsequently many abnormal Type 2 cells are seen. Some are binucleate, and others show nuclear disruption. The usual process of differentiation to Type 1 cells does not occur; instead, a variety of epithelial forms are found, including fetal-like tubular structures and ciliated and squamous metaplastic cells. The correlation of epithelial injury and repair with the direct demonstration of bleomycin in the lung indicates that Type 2 cells are susceptible to injury in the division and differentiation phases of the cell cycle and may then produce a variety of inappropriate alveolar lining cells.