Polunovsky V A, Chen B, Henke C, Snover D, Wendt C, Ingbar D H, Bitterman P B
Department of Medicine, University of Minnesota Medical School, Minneapolis 55455.
J Clin Invest. 1993 Jul;92(1):388-97. doi: 10.1172/JCI116578.
Repair after acute lung injury requires elimination of granulation tissue from the alveolar airspace. We hypothesized that during lung repair, signals capable of inducing the death of the two principal cellular elements of granulation tissue, fibroblasts and endothelial cells, would be present at the air-lung interface. Bronchoalveolar lavage fluid obtained from patients during lung repair induced both fibroblast and endothelial cell death, while fluid obtained at the time of injury or from patient controls did not. The mode of cell death for endothelial cells was apoptosis. Fibroblast death, while morphologically distinct from necrosis, also differed from typical apoptosis. Only proliferating cells were susceptible to the bioactivities in lavage fluid, which were trypsin sensitive and lipid insoluble. Histological examination of lung tissue from patients after lung injury revealed evidence of apoptotic cells within airspace granulation tissue. Our results suggest that cell death induced by peptide(s) present at the air-lung interface may participate in the remodeling process that accompanies tissue repair after injury.
急性肺损伤后的修复需要清除肺泡气腔内的肉芽组织。我们推测，在肺修复过程中，能够诱导肉芽组织的两种主要细胞成分（成纤维细胞和内皮细胞）死亡的信号会出现在气-肺界面。在肺修复过程中从患者获取的支气管肺泡灌洗液可诱导成纤维细胞和内皮细胞死亡，而在损伤时或从患者对照组获取的液体则无此作用。内皮细胞的细胞死亡方式为凋亡。成纤维细胞死亡虽然在形态上与坏死不同，但也与典型的凋亡不同。只有增殖细胞对灌洗液中的生物活性敏感，这些生物活性对胰蛋白酶敏感且不溶于脂质。对肺损伤后患者的肺组织进行组织学检查发现，气腔肉芽组织内有凋亡细胞的证据。我们的结果表明，存在于气-肺界面的肽诱导的细胞死亡可能参与损伤后组织修复所伴随的重塑过程。
