Leslie C C, McCormick-Shannon K, Cook J L, Mason R J
Am Rev Respir Dis. 1985 Dec;132(6):1246-52. doi: 10.1164/arrd.1985.132.6.1246.
Proliferation of alveolar type II cells after lung injury is crucial for repair of the epithelium. Because an influx of macrophages occurs as part of the inflammatory response associated with acute lung injury and macrophages produce mitogenic factors for a variety of cell types, experiments were conducted to determine if macrophages stimulated DNA synthesis in type II cells. Dialyzed medium conditioned by macrophages consistently stimulated type II cell DNA synthesis, whereas medium conditioned by a variety of other cell types did not. A SV40-transformed macrophage cell line, produced in our laboratory, also secreted substance(s) that enhanced 3H-thymidine incorporation into type II cells. In addition, coculturing rat alveolar macrophages with type II cells stimulated DNA synthesis in the epithelial cells. As determined by autoradiography, the addition of macrophages to type II cells cultured on plastic or on an endothelial cell extracellular matrix increased the labeling index of the epithelial cells from 1 to 15% and from 19 to 51%, respectively. The culture conditions that promoted the greatest increase in DNA synthesis, as well as an increase in cell number, occurred with type II cells plated on an extracellular matrix in medium containing macrophage-conditioned medium, cholera toxin, insulin, and epidermal growth factor. The results suggest that substances secreted by macrophages play a role in regulating alveolar type II cell proliferation in vivo.
肺损伤后肺泡II型细胞的增殖对于上皮修复至关重要。由于巨噬细胞的流入是急性肺损伤相关炎症反应的一部分，且巨噬细胞会产生多种细胞类型的促有丝分裂因子，因此开展了实验以确定巨噬细胞是否刺激II型细胞的DNA合成。经巨噬细胞处理的透析培养基持续刺激II型细胞的DNA合成，而经多种其他细胞类型处理的培养基则无此作用。我们实验室构建的一种SV40转化巨噬细胞系也分泌能增强3H-胸腺嘧啶核苷掺入II型细胞的物质。此外，将大鼠肺泡巨噬细胞与II型细胞共培养可刺激上皮细胞的DNA合成。通过放射自显影测定，向培养在塑料或内皮细胞细胞外基质上的II型细胞中添加巨噬细胞，上皮细胞的标记指数分别从1%增加到15%以及从19%增加到51%。在含有巨噬细胞条件培养基、霍乱毒素、胰岛素和表皮生长因子的培养基中，将II型细胞接种在细胞外基质上时，出现了促进DNA合成增加以及细胞数量增加的培养条件。结果表明，巨噬细胞分泌的物质在体内调节肺泡II型细胞增殖中发挥作用。
