EXPRESSION OF P53, P21 (WAF1 CIP1/SDI1) AND FAS ANTIGEN IN COLLAGEN VASCULAR AND GRANULOMATOUS LUNG-DISEASES/

Fas is expressed in various cells and transduces the cell death signal . p21 is a mediator of p53-dependent G(1) arrest associated with deoxy ribonucleic acid (DNA) damage. The upregulation of p53 and p21 associa ted with DNA damage in idiopathic pulmonary fibrosis has been describe d previously. In this study, p53, p21, and Fas expression and DNA dama ge were examined in interstitial pneumonia associated with collagen va scular diseases (CVD-IP). DNA damage was assessed by terminal deoxynuc leotidyl transferase-mediated deoxyuridine triphosphate biotin nick en d-labelling (TUNEL) and p53, p21 and Fas proteins were detected by imm unohistochemistry in 13 cases of CVD-IP, 13 of sarcoidosis, seven of h ypersensitivity pneumonitis (HP) and eight control patients with norma l lung parenchyma. TUNEL-positive signals were found in bronchiolar or alveolar epithelial cells in 11 of 13 (85%) specimens of CVD-IP, but not in sarcoidosis, HP or controls, except for a case of chronic HP wi th pulmonary fibrosis. p53, p21 and Fas were detected in bronchiolar o r alveolar epithelial cells in nine (69%), 10 (77%) and 12 (92%) of 13 specimens of CVD-IP, respectively, but not in sarcoidosis, HP or cont rols, except for a case of chronic HP. These results suggest that the upregulation of p53, p21 and Fas in bronchiolar and alveolar epithelia l cells associated with deoxyribonucleic acid damage may participate i n the process of pulmonary fibrosis in interstitial pneumonia associat ed with collagen vascular diseases and chronic hypersensitivity pneumo nitis.