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 alve olar epithelium and for restoration after lung injury, Although variou s known growth factors have been reported to stimulate type LI cell pr oliferation in vitro, there is very little knowledge on which growth f actors are present in the lung in vivo. We have previously reported th at 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 seque ntial chromatography on blue Sepharose and heparin Sepharose. Hepatocy te growth factor (HGF) and acidic fibroblast growth factor were detect ed in the partially purified lavage fluid by Western analysis. The amo unt of HGF recovered by lavage was similar to 6 ng/rat. By use of neut ralizing 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. Final ly, we have demonstrated that much of the mitogenic activity in salt e xtracts of human lung is HGF. We conclude that HGF is found in rat lav age fluid and is possibly an important mitogen for adult type II cells in vivo.