INSERM U1100, Pathologies Pulmonaires: Protéolyse et Aérosolthérapie, Equipe 2: Mécanismes Protéolytiques dans l'Inflammation; Faculté de Médecine, Centre d'Etude des Pathologies Respiratoires (CEPR), Université François Rabelais, Tours, France.
Proteomics Clin Appl. 2014 Jun;8(5-6):447-53. doi: 10.1002/prca.201300047. Epub 2013 Nov 25.
Human idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disorder with a poor prognosis. The identification of a new and specific biomarker in bronchoalveolar lavage fluids (BALFs) may assist in the diagnosis of the disease.
Characterization of cysteine Cats and their endogenous inhibitor, cystatin C, was conducted by immunochemical analysis and measurement of endopeptidase activity of control (n = 11) and IPF (n = 25) BALFs (normalized conditions, 20 μg protein/assay).
Cathepsin (Cat) B was detected as proform and mature enzyme for both control and IPF samples, while Cats K, L, and S were found as zymogens with a strengthened staining in IPF BALFs. The overall endopeptidase activity related mainly to Cat B and did not vary significantly between control and IPF samples. Conversely a significant increase of immunoreactive cystatin C was measured in BALFs for each of three IPF grades.
An excessive deposition of extracellular matrix proteins is the hallmark of fibrotic disorders. Cats are potent collagenases and might be essential for lung homeostasis. Taken together, increase of cystatin C in IPF BALFs may reflect abnormal regulation of proteolytic activity of Cats in lung, which in turn can promote the development of fibrosis.
人类特发性肺纤维化（IPF）是一种进行性间质性肺疾病，预后不良。在支气管肺泡灌洗液（BALF）中鉴定新的特异性生物标志物，可能有助于疾病的诊断。
通过免疫化学分析和内肽酶活性测定，对控制组（n=11）和 IPF 组（n=25）BALF（标准化条件，20μg 蛋白/分析）中的半胱氨酸 Cats 及其内源性抑制剂胱抑素 C 进行了表征。
Cathepsin (Cat) B 在对照和 IPF 样本中均被检测为前体酶和成熟酶，而 Cats K、L 和 S 则被发现为无活性酶原，在 IPF BALF 中染色增强。总的内肽酶活性主要与 Cat B 相关，在对照和 IPF 样本之间没有显著差异。相反，在每个 IPF 等级的 BALF 中，免疫反应性胱抑素 C 的测量值都显著增加。
细胞外基质蛋白的过度沉积是纤维化疾病的特征。Cats 是有效的胶原蛋白酶，可能对肺的内稳态至关重要。综上所述，IPF BALF 中胱抑素 C 的增加可能反映了肺中 Cats 蛋白水解活性的异常调节，进而促进纤维化的发展。
