CYTOSKELETAL PROTEIN MODULATION IN PULMONARY ALVEOLAR MYOFIBROBLASTS DURING IDIOPATHIC PULMONARY FIBROSIS - POSSIBLE ROLE OF TRANSFORMING GROWTH-FACTOR-BETA AND TUMOR-NECROSIS-FACTOR-ALPHA

Pulmonary biopsy specimens from ten cases of idiopathic pulmonary fibr osis (IPF) were examined using routine histological stains, including toluidine blue, and immunohistochemistry by means of specific anti bod ies against alpha-smooth muscle (alpha-SM) actin, desmin, keratin, TGF beta 1, and TNF alpha. The sections were compared with two cases of n ormal lung. As shown previously, normal alveolar interstitium did not contain alpha-SM actin positive myofibroblasts nor did the alveolar li ning contain any significant number of TGF beta 1 or TNF alpha laden e pithelial cells. In IPF, du ring the inflammatory stage, the alveolar myofibroblasts expressed alpha-SM actin and the regenerating type II a lveolar epithelium stained strongly with TGF beta 1 and TNF alpha anti bodies. The former cytokine was also detected in the interstitial matr ix and fibroblastic cells as well as in the wall of vessels. At this s tage, a manifest mast cell infiltration was noted. In very fibrotic an d cystic alveolar tissue, i.e., at end stage fibrosis, the number of a lpha-SM actin positive myofibroblasts as well as that of TNF alpha lad en type II epithelial cells diminished, while TGF beta 1 positive cell s persisted. Our findings demonstrate that during IPF alveolar type II epithelium constitutes, if not the site of synthesis, at least the ma in reservoir for TGF beta 1 and TNF alpha. These cytokines, besides th eir involvement in fibrogenesis, play probably an important role in th e expression of alpha-SM actin by alveolar myofibroblasts Our study su ggests the possibility of an interaction between interstitial cells an d alveolar epithelium, during IPF.