Induction of EGF receptor and erbB-2 during endotoxin-induced alveolar type II cell proliferation in the rat lung

The overall purpose of this study was to produce a model of transient type II cell hyperplasia to enable comparisons of changes in gene expression in the remodelling epithelium with those in carcinogen-induced hyperplastic lesions. Rats instilled with endotoxin had increased numbers of neutrophils in the bronchoalveolar lavage fluid (BALF) by 3 hours that reached maximum levels at 48 hours and returned to background levels 168 hours after instillation. The number of macrophages in the BALF increased throughout the 168 hours following instillation. Epithelial cell hyperplasia was maximum at 96 hours post-instillation in areas of extensive inflammation. The number of alveolar epithelial cells that exhibited bromodeoxyuridine nuclear incorporation reached maximum levels 48 hours after endotoxin treatment and decreased to near background levels at 96 hours. Ultrastructural studies of hyperplastic cells showed the presence of lamellar bodies and condensed chromosomes, characteristics of type II cells in mitosis. At 168 hours after instillation, the hyperplasia regressed to form normal-appearing alveolar structure with few focal lesions. Specific immunostaining for the proto-oncogenes, EGF receptor and erbB-2, on tissue sections increased during the endotoxin-induced hyperplasia. Furthermore, the induction of the 170 kDa and 180 kDa glycoproteins in type II cells isolated from endotoxin-instilled rats was shown by Western analysis. These proto-oncogenes, often thought to be markers of early events during neoplasia, may, therefore, also be associated with wound repair mechanisms after hyperplasia.