HEPATOCYTE GROWTH-FACTOR IS A GROWTH-FACTOR FOR RAT ALVEOLAR TYPE-II CELLS

Proliferation of alveolar type II cells is thought to be critical for restoration of gas exchange units after diffuse alveolar damage. Howev er, the factors that regulate type II cell proliferation are not well understood. Hepatocyte growth factor (HGF) is a potentially important mitogen because it causes epithelial cells but not fibroblasts to prol iferate and is found in the lung. We used rat alveolar type II cells i n primary culture to demonstrate that HGF stimulates DNA synthesis in a concentration-dependent manner. The half maximal effect on stimulati on of thymidine incorporation was less than 1 ng/ml. By autoradiograph y, HGF increased nuclear labeling from 1.3% of type II cells with medi um alone to 9.4% with 5 ng/ml HGF. During this time, HGF modestly incr eased cell number in comparison to control media. However, in an assay of colony formation in low-density cultures, HGF did not consistently increase colony formation by alveolar type II cells and was less effe ctive than acidic fibroblast growth factor or bronchoalveolar lavage f luid in this assay. The receptor for HGF (c-met proto-oncogene) was ex pressed in rat type II cells and whole lung but not in macrophages. In contrast, the mRNA for HGF was detected in rat macrophages and lung b ut not in type II cells. However, HGF message was not detected in huma n alveolar macrophages under conditions in which the HGF message was d etected in rat alveolar macrophages and in human fibroblasts. Hence, H GF is a potential paracrine growth factor for alveolar type II cells, but there may be important species differences in the relative level o f expression.