A study on diffuse alveolar damage and ubiquitin-positive pneumocytes in the elderly

Aim: The ubiquitin proteasome system (UFS) is important because homeostasis through proteolysis and ubiquitin (Ub) has been observed to appear in diseases of the central nervous system. However, studies on UPS in relation to pulmonary diseases are few and no other investigators have described Ub-positive cells in the lung. Intracytoplasmic eosinophilic inclusion bodies in pneumocytes have been known to appear in cases of diffuse alveolar damage (DAD). We found that these inclusion bodies in DAD were positive for Ub. In this study, DAD cases in the elderly were studied to clarify the relationship between Ub-positive cells and cellular damage in the lungs. Methods: Representative lung fields from a total of 26 patients with DAD were studied immunohistochemically, using Ub staining. The severity of DAD was evaluated after each case was scored for hyaline membrane formation and lung injury, respectively. Non-DAD diseases from 19 autopsy cases were studied as controls. The mean age of both groups was 72.1. Results: Variably sized and shaped eosinophilic inclusion bodies were found in 7 cases (26.9%) of the DAD cases (inclusion body group) and all inclusion bodies were positive for Ub and cytokeratin KL-1. Pneumocytes without inclusion bodies were occasionally positive for Ub, with an intracytoplasmic granular pattern, not only in the inclusion body group but also in the non-inclusion body group (4 of DAD cases). These Ub-positive cells (both Ub-positive inclusion bodies and the granular Ub-positive cells) were found to have high rate of hyaline membrane formation and lung injury in the DAD cases. Conclusion: Elderly DAD cases had Ub-positive inclusion bodies in pneumocytes and Ub-positive pneumocytes were found with or without the inclusion bodies in DAD. This means that accumulation of ubiquitinated protein including cytokeratin could be recognized as inclusion bodies in pneumocytes. The presence of these Ub-positive cells might be a morphological indicator for evaluation of cellular damage in the patients with DAD.