KERATINOCYTE GROWTH-FACTOR IS A GROWTH-FACTOR FOR TYPE-II PNEUMOCYTESIN-VIVO

Keratinocyte growth factor (KGF) administered as a single intratrachea l injection causes a prominent dose-dependent proliferation of type II alveolar epithelial cells in the lungs of adult rats. The increase in mitotically active alveolar cells histologically appears as a micropa pillary epithelial cell hyperplasia after 2 d and peaks after 3 d in t he form of monolayers of cuboidal epithelial cells lining alveolar sep tae. Proliferating cell nuclear antigen immunohistochemistry confirmed the profound proliferative response induced by KGF. The hyperplastic alveolar lining cells contain immunoreactive surfactant protein B and are ultrastructurally noted to contain lamellar inclusions characteris tic of surfactant-producing type II pneumocytes. Mild focal bronchiola r epithelial hyperplasia is noted but is much less striking than the p roliferation of type II pneumocytes. Large airways are unaffected by K GF. Daily intravenous injection of KGF is also able to cause pneumocyt e proliferation. The normal adult rat lung constitutively expresses bo th KGF and KGF receptor mRNA, suggesting that endogenous KGF may be im plicated in the paracrine regulation of the growth of pneumocytes. In conclusion, I(GF rapidly and specifically induces proliferation and di fferentiation of type II pneumocytes in the normal adult lung.