Tenascin mRNA expression at the foci of recent injury in usual interstitial pneumonia

To elucidate which cells are synthesizing tenascin in usual interstitial pn eumonia (UIP) we have analyzed thoracoscopic or open lung biopsies from 30 patients with UIP by mRNA in situ hybridization, using S-35-labeled tenasci n RNA probes. The phenotype of the cells expressing tenascin mRNA was confi rmed by immunohistochemical stainings of serial sections with antibodies ag ainst alpha-smooth muscle actin and human cytokeratin. The results demonstr ate that tenascin is expressed at the foci of recent lesions consisting of intralumenal or incorporating loose fibrotic buds. The cells expressing ten ascin mRNA were located in and underneath the newly formed epithelium. Immu nohistochemical stainings showed that the cells in the newly formed epithel ium were strongly cytokeratin positive, and thus evidently regenerating typ e 2 pneumocytes, while the cells underneath the newly formed epithelium wer e alpha-smooth muscle actin positive and apparently myofibroblasts. Tenasci n mRNA expression was clearly stronger and more frequent in myofibroblasts than in type 2 pneumocytes, however. Weak tenascin mRNA expression was also found in metaplastic bronchiolar-type epithelium and alveolar macrophages. Our results are thus in good agreement with the previous studies showing t hat tenascin is actively synthesized at the early fibrotic lesions in UIP. Furthermore, results demonstrate that the interaction between the epitheliu m and the underlying connective tissue plays a significant role in tenascin synthesis and that myofibroblasts are mainly responsible for its synthesis in fibroblastic foci of UIP.