Hepatocyte growth factor is a mitogen for alveolar type ii cells in rat lavage fluid. Mason, Robert J., Kathleen McCormick-Shannon, Jeffrey S. Rubin, Toshikazu Nakamura, Christina C. Leslie. Departments of Medicine and Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado, Departments of Pathology and Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, Laboratory of Cellular & Molecular Biology, National Cancer Institute
APStracts 3:0025L, 1996.
Proliferation of type II cells is required for maintenance of the alveolar epithelium and for restoration after lung injury. Although a variety of known growth factors have been reported to stimulate type II 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 biologic 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 (aFGF, FGF-1) were detected in the partially purified lavage fluid by Western analysis. The amount of HGF recovered by lavage was about 6 ng/rat. By use of neutralizing antibodies for different growth factors, HGF was found to be responsible for most of the stimulatory activity for rat type II 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 to be an important mitogen for adult type II cells in vivo. 

Received 5 June 1995; accepted in final form 15 January 1996.
APS Manuscript Number L174-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96