Hepatocyte growth factor is a mitogen for alveolar type II cells in rat lavage fluid

Proliferation of type II cells is required for maintenance of the alveolar epithelium and for restoration after lung injury, Although various known growth factors have been reported to stimulate type LI cell proliferation in vitro, there is very little knowledge on which growth factors are present in the lung in vivo. We have previously reported that rat lavage fluid contains a mitogen(s) for type II cells, and this study was designed to identify the growth factor(s) in this biological fluid for type II cells. The mitogenic activity was purified by sequential chromatography on blue Sepharose and heparin Sepharose. Hepatocyte growth factor (HGF) and acidic fibroblast growth factor were detected in the partially purified lavage fluid by Western analysis. The amount of HGF recovered by lavage was similar to 6 ng/rat. By use of neutralizing antibodies for different growth factors, HGF was found to he responsible for most of the stimulatory activity for rat type a cells in the partially purified lavage fluid. In addition to HGF, rat lavage fluid also contained potent mitogenic activity for fibroblasts. Finally, we have demonstrated that much of the mitogenic activity in salt extracts of human lung is HGF. We conclude that HGF is found in rat lavage fluid and is possibly an important mitogen for adult type II cells in vivo.