INDUCTION OF TENASCIN IN RAT LUNGS UNDERGOING BLEOMYCIN-INDUCED PULMONARY FIBROSIS

Lung injury induced by bleomycin is associated with early inflammation and subsequent excessive deposition of extracellular matrix. In the p resent study, we investigated the expression of extracellular matrix g lycoprotein tenascin (TN) during pulmonary injury induced by bleomycin . After the initial lung injury induced by intratracheal bleomycin ins tillation, TN and collagen type III(COL III) mRNAs were greatly induce d. The pattern of induction of TN was distinct from that of COL III. T N was primarily induced during the early inflammatory phase, whereas t he increase in COL III synthesis continued during the reparative phase . The induction and localization of TN mRNA during bleomycin-induced p ulmonary injury were also examined by in situ hybridization. TN mRNA w as focally induced in rat lungs 3 days after bleomycin administration. Induction of TN mRNA was spatially restricted in the areas of tissue inflammation. The interstitial cells in alveolar septal walls and seco ndary septal tips in the areas of tissue damage were the major source of TN mRNA production. Expression of TN mRNA was decreased as the infl ammation attenuated and development of fibrosis proceeded. Immunocytoc hemical analyses of TN protein distribution in the lung yielded corrob orative results. Immunoreactive TN protein was found in a patchy distr ibution in alveolar septal walls and secondary septal tips in the area s of damaged tissues. This study demonstrated that TN is a unique earl y-response extracellular matrix component to bleomycin-induced pulmona ry injury and is induced at the sites of the inflammation, suggesting a potential role of TN as a modulator of pulmonary inflammation and re pair.