Cathepsin H and napsin A are active in the alveoli and increased in alveolar proteinosis

Abstract

Pulmonary alveolar proteinosis (PAP) is a group of rare diseases with disturbed homeostasis of alveolar surfactant. While 90% of the primary adult forms are caused by granulocyte-macrophage colony-stimulating factor autoantibodies, the underlying cause of the juvenile form remains unknown. In order to distinguish primary from secondary effects in the pathogenesis of these two forms, the present authors studied the surfactant protein processing proteases napsin A and cathepsin H.In total, 16 controls, 20 patients with juvenile PAP and 13 adults with idiopathic PAP were enrolled. Amounts and activities of the proteases in the bronchoalveolar lavage fluid (BALF) were determined by immunoblotting and specific substrate cleavage.Both proteases were present and active in BALF from controls and increased in juvenile and adult PAP patients. The amount of active cathepsin H in relation to total cathepsin H was increased in PAP patients compared with controls. Cystatin C, the physiological inhibitor of cathepsin H in the alveolar space, was not increased to the same degree as cathepsin H, resulting in an imbalance of inhibitor to protease in the alveolar space.A general defect in napsin A or cathepsin H expression or activity was not the specific cause for abnormal surfactant accumulation in juvenile pulmonary alveolar proteinosis.

Immunohistochemical Comparison of Ovarian and Uterine Endometrioid Carcinoma, Endometrioid Carcinoma With Clear Cell Change, and Clear Cell Carcinoma

“…37 Napsin A is a functional aspartic proteinase involved in the maturation of surfactant protein B. It is normally expressed in type II pneumocytes, alveolar macrophages, renal tubules, exocrine glands, and pancreatic ducts 38,39 and has been used in the diagnostic setting to help classify pulmonary and renal carcinomas. [40][41][42] Recent studies have described Napsin A immunoreactivity in certain gynecologic malignancies.…”

Serum Cystatin C and Emphysema: Results from the National Health and Nutrition Examination Survey (NHANES)

“…It has been demonstrated in animal studies that the capacity of CysC to neutralize excessive local proteolytic activity of the cathepsins might be limited in the lung [26]. CysC might not achieve sufficient levels in the microenvironment of the alveolar macrophage where cathepsins are released by lysosomes [43]. In addition, CysC has affinity to primarily cathepsin B; other cathepsins might be less inhibited by CysC and might contribute to tissue destruction.…”

Evaluation of Napsin A, Cytokeratin 5/6, p63, and Thyroid Transcription Factor 1 in Adenocarcinoma Versus Squamous Cell Carcinoma of the Lung

“…It is a single-chain protein that is normally expressed in type II pneumocytes, alveolar macrophages, renal tubules, exocrine glands, and pancreatic ducts. [15][16][17] The role of napsin A in differentiating primary from metastatic ACA of the lung has previously been reported. 12,15,18,19 Positive immunohistochemical staining shows intense granular cytoplasmic reactivity.…”