ASSOCIATION OF P53 AND WAF1 EXPRESSION WITH APOPTOSIS IN DIFFUSE ALVEOLAR DAMAGE

Little is known about alterations in cell cycle regulatory proteins su ch as p53 and WAF1 in diffuse alveolar damage (DAD). We hypothesized t hat upregulation of p53 and WAF1 in type II pneumocytes in DAD is asso ciated with underlying DNA damage and apoptosis. Twenty cases of DAD a nd twenty control specimens of lung adjacent to resected tumors were s tudied Immunohistochemical stains with antibodies recognizing p53 and WAF1 were performed, and apoptosis was assessed in sixteen cases by th e nick end-labeling method. We identified p53 expression and apoptosis in all cases of DAD but not in any of the control lungs We detected W AF1 expression at nineteen of twenty cases of DAD and in sixteen of tw enty control lungs. In general the distribution and intensity of WAF1 staining were greater in DAD than in control lungs. Staining for both p53 and WAF1 and labeling of apoptotic cells in DAD were usually focal (<10% of cells) and predominantly localized in type II pneumocytes. W e conclude that increased p53 and WAF1 expression in DAD reflects norm al physiological up-regulation in response to cellular and DNA damage and is associated with apoptosis of type II pneumocytes. p53-dependent apoptosis may contribute to the pathogenesis of this disease.