Aspartic Proteinases in Normal Lung and Interstitial Pulmonary Diseases

Abstract

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.

Gene Expression Profiling of Progressive Papillary Noninvasive Carcinomas of the Urinary Bladder

“…CTSE is an intracellular aspartic protease that can be found at the gastric surface (42), in neuronal cells, and is also expressed at the infiltration zone of gastric carcinomas (43), cervical adenocarcinomas (44), and pancreatic ductal carcinomas (45). CTSE is suspected to be involved in the execution of neuronal death pathways (46) and parenchymal remodeling that occurs in fibrosing lung disease (47). It also has a role in antigen processing by hydrolyzing antigenic peptides and the invariant chain (CD74) which influences the expression and peptide loading of MHC II molecules in professional and nonprofessional antigen-presenting cells Abbreviations: OS, overall survival; PFS, progression-free survival; RFS, recurrence-free survival.…”

Wound healing and fibrosis in intestinal disease

“…Cathepsin family members are involved in the remodelling of ECM proteins under inflammatory conditions. 45 Cathepsins L and E degrade collagen and elastin, and have a role in the pathogenesis of artheriosclerosis and lung emphysema/fibrosis. 45 Destruction of elastin-rich tissue is furthermore associated with local accumulation of macrophages containing high levels of cathepsins B and L. The aspartic proteinase cathepsin D also has the potential to initiate a proteolytic cascade, and to degrade and remodel ECM.…”

Cathepsin E Deficiency Induces a Novel Form of Lysosomal Storage Disorder Showing the Accumulation of Lysosomal Membrane Sialoglycoproteins and the Elevation of Lysosomal pH in Macrophages

“…In antigen presenting cells, such as macrophages and microglia, cathepsin E is mainly localized in the endosomal compartment (2,3). Previous studies have demonstrated that cathepsin E is important for exogenous antigen processing via the major histocompatibility complex class II presenting system (3)(4)(5) and is increasingly expressed in inflammatory cells within and nearby carcinomas (6), Clara cells, and the reactive type II pneumocytes (7,8). Recent gene or protein expression profiles have demonstrated the increased expression of cathepsin E in several types of carcinomas (9 -12), which is significantly associated with survival.…”