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 lung, 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 bronchial cells overlying lymphoid follicles, no other CathE-immunoreactive cell was found in the lung. Immunoblots of crude protein extracts of lung tissue using PgII and CathE antibodies showed reactivity with single molecular species co-migrating with analogous bands obtained from gastric mucosa (molecular weight, 40,500 for PgII and 42,000 to 44,000 for CathE). In 75 cases of non-neoplastic lung disease, a highly significant correlation was found between the severity of histopathologic lesions and expression of both PgII (P < 0.001) and CathE (P < 0.001). Epithelial hyperplasia contributed more than inflammation and fibrosis to this relationship. Proteinase overexpression was not specific to any particular disease and was found in both focal and diffuse lesions. Segregation of PgII and CathE in different cells was lost in hyperplastic epithelium, where coexpression of both proteinases by the same cell was frequently observed. The location of both proteinases in distal airways and their enhanced expression in the proliferative, hyperplastic phase of several non-neoplastic pneumopathies suggest their possible involvement in the process of parenchymal remodeling that occurs in fibrosing lung diseases.
Bosi
F
F
Department of Pathology, University of Pavia, Italy.
Silini
E
E
Luisetti
M
M
Romano
A M
AM
Prati
U
U
Silvestri
M
M
Tinelli
C
C
Samloff
I M
IM
Fiocca
R
R
D020059:Cathepsin E; D002403:Cathepsins / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D008168:Lung / Q000166:cytology / Q000201:enzymology*; D010435:Pepsinogens / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000201:enzymology*
D010435:Pepsinogens; D002403:Cathepsins; D020059:Cathepsin E