Overexpression of surfactant protein SP-A, SP-B, and SP-C mRNA in rat lungs with lipopolysaccharide-induced injury.
Overexpression of surfactant protein SP-A, SP-B, and SP-C mRNA in rat lungs with lipopolysaccharide-induced injury.
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发表时间：
1996
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通讯作者：
K. Sugahara;K. Iyama;Kimihiko Sano;Yoshio Kuroki;Toyoaki Akino;M. Matsumoto
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作者：
K. Sugahara;K. Iyama;Kimihiko Sano;Yoshio Kuroki;Toyoaki Akino;M. Matsumoto
肺泡上皮细胞的再生是许多肺损伤的重要修复过程之一。我们已经研究了组织病理学和表面活性蛋白A（SP-A），SP-B，SP-C mRNA的基因表达的顺序分析肺泡II型细胞与脂多糖诱导（LPS诱导）肺损伤。小剂量（1至2毫克/公斤）的LPS注射到成年大鼠的气管内滴注，并在一段时间后，肺进行检查，使用光学和电子显微镜，免疫组化研究，使用抗溴脱氧尿苷（抗BrdU）和抗SP-A抗体，并在原位杂交使用类型特异性，表面活性剂cDNA探针。还进行了北方印迹分析。LPS给药后3 ~ 7天，肺泡间隔增厚，上皮细胞和间质细胞数量增加。BrdU掺入细胞的数量明显增加，在这些地区，许多肺泡上皮细胞胞内免疫反应抗SP-A抗体，用电子显微镜检查发现许多板层体。通过原位杂交，SP-A，SP-B和SP-C mRNA的放射自显影银颗粒的数量显着增加，在肺泡II型上皮细胞从LPS给药的大鼠肺。肺泡上皮细胞表面活性物质基因表达对LPS的反应似乎比细支气管上皮细胞更强。通过北方印迹分析，SP-A、SP-B和SP-C mRNA的相对丰度在LPS给药的肺中也较高，并且与原位杂交的结果良好相关。目前的研究表明，LPS的肺内给药诱导肺泡上皮细胞的显着增殖与SP-A，SP-B，SP-C mRNA的同时增加，以及SP-A的生产在肺损伤的早期反应。提示肺泡上皮细胞的增殖和分化在急性肺损伤后受损肺泡的修复过程中起重要作用。
Regeneration of alveolar epithelial cells is one of the important repair processes in many types of lung injury. We have examined sequential analysis of histopathology and gene expressions of surfactant protein A (SP-A), SP-B, and SP-C mRNA in alveolar type II cells of rats with lipopolysaccharide-induced (LPS-induced) lung injury. A small dose (1 to 2 mg/kg) of LPS was injected by intratracheal instillation in adult rats, and after a given period, the lungs were processed for examination using light and electron microscopy, for immunohistochemical study using anti-bromodeoxyuridine (anti-BrdU) and anti-SP-A antibodies, and for in situ hybridization using type-specific, surfactant cDNA probes. Northern blot analysis was also performed. From 3 to 7 days after LPS administration, alveolar septa were thickened, with increased numbers of epithelial and interstitial cells. BrdU-incorporated cells apparently increased in number in these areas, and many alveolar epithelial cells were intracellularly immunoreactive to anti-SP-A antibody, with many lamellar bodies found on examination using electron microscopy. By in situ hybridization, the number of autoradiographic silver grains for SP-A, SP-B, and SP-C mRNA increased strikingly, in alveolar type II epithelial cells of the lungs from LPS-administered rats. These responses of surfactant gene expression to LPS seemed to be stronger in alveolar epithelial cells than in the bronchiolar epithelium. By Northern blot analysis, the relative abundances of SP-A, SP-B, and SP-C mRNA were also higher in the LPS-administered lungs and correlated well with the results of in situ hybridization. The present study demonstrates that intratracheal administration of LPS induces the marked proliferation of alveolar epithelial cells in association with the concurrently increased SP-A, SP-B, and SP-C mRNA, as well as the SP-A production in the early response to lung injury. These results suggest that proliferation and differentiation of alveolar epithelial cells may play important roles in the repair process of the damaged alveoli after acute lung injury.