ASPARTIC PROTEINASES IN NORMAL LUNG AND INTERSTITIAL PULMONARY-DISEASES

Two aspartic proteinases, pepsinogen II (PgII) and cathepsin E (CathE) , were identified immunocytochemically in lung epithelia. In normal lu ng, type II pneumocytes were characterized by PgII immunoreactivity of variable intensity, while bronchiolar Clara cells reacted with CathE antibodies. With the exception of small groups of nonciliated bronchia l cells overlying lymphoid follicles, no other CathE-immunoreactive ce ll was found in the lung. Immunoblots of crude protein extracts of lun g tissue using PgII and CathE antibodies showed reactivity with single molecular species co-migrating with analogous bands obtained from gas tric mucosa (molecular weight, 40,500 for PgII and 42,000 to 44,000 fo r CathE). In 75 cases of non-neoplastic lung disease, a highly signifi cant correlation was found between the severity of histopathologic les ions and expression of both PgII (P < 0.001) and CathE (P < 0.001). Ep ithelial hyperplasia contributed more than inflammation and fibrosis t o this relationship. Proteinase overexpression was not specific to any particular disease and was found in both focal and diffuse lesions. S egregation of PgII and CathE in different cells was lost in hyperplast ic epithelium, where coexpression of both proteinases by the same cell was frequently observed. The location of both proteinases in distal a irways and their enhanced expression in the proliferative, hyperplasti c phase of several non-neoplastic pneumopathies suggest their possible involvement in the process of parenchymal remodeling that occurs in f ibrosing lung diseases.