Acharya Pinak S, Zukas Alicia, Chandan Vishal, Katzenstein Anna-Luise A, Puré Ellen
Department of Medicine, Division of Pulmonary, Allergy and Critical Care, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
Hum Pathol. 2006 Mar;37(3):352-60. doi: 10.1016/j.humpath.2005.11.020.
Fibroblast activation protein (FAPalpha) is a member of the cell surface dipeptidyl peptidase (DPP) family of serine proteases. In its dimer form, FAPalpha exhibits gelatinase, collagenase, and DPP activity in vitro. Reactive fibroblasts in healing wounds and stromal fibroblasts associated with epithelial tumors express FAPalpha. Idiopathic pulmonary fibrosis (IPF) is a disease of the lung characterized by progressive fibrosis with no clear etiology or molecular marker for disease activity. Recently, it has been shown that fibroblast FAPalpha expression is induced in liver cirrhosis, with an expression pattern distinct from alpha-smooth muscle actin (alpha-SMA). In this study, we determine whether FAPalpha expression is selectively induced in areas of ongoing tissue remodeling characterized by fibroblast foci in IPF. Human lung tissue was obtained from patients with IPF, centrilobular emphysema, and normal lung. Immunohistochemical studies were performed using anti-FAPalpha antibody and antibodies against alpha-SMA and CD26 (DPPIV), another member of the DPP family. We found that FAPalpha was not expressed in normal human lung tissue or tissue with evidence of centriacinar emphysema, but was induced in all patients with IPF and With a pattern distinct from that of CD26 found primarily on hyperplastic alveolar epithelium. Specifically, FAPalpha was detected in fibroblast foci and in fibrotic interstitium and not in the interstitium of adjacent architecturally normal lung. Alveolar/airway epithelium and vascular smooth muscle did not express FAPalpha. This is the first report of FAPalpha expression in IPF and our results suggest that FAPalpha is selectively induced in fibrotic foci, but not in normal or emphysematous lung. Future studies will address whether FAPalpha may be used as a marker for disease activity in IPF.
成纤维细胞活化蛋白（FAPα）是细胞表面丝氨酸蛋白酶二肽基肽酶（DPP）家族的成员。以其二聚体形式，FAPα在体外表现出明胶酶、胶原酶和DPP活性。愈合伤口中的反应性成纤维细胞以及与上皮肿瘤相关的基质成纤维细胞表达FAPα。特发性肺纤维化（IPF）是一种肺部疾病，其特征为进行性纤维化，病因不明且无明确的疾病活动分子标志物。最近研究表明，肝硬化中可诱导成纤维细胞FAPα表达，其表达模式与α平滑肌肌动蛋白（α-SMA）不同。在本研究中，我们确定在IPF中以成纤维细胞灶为特征的正在进行组织重塑的区域是否选择性诱导FAPα表达。从IPF、小叶中心型肺气肿和正常肺患者获取人肺组织。使用抗FAPα抗体以及抗α-SMA和CD26（DPPIV，DPP家族的另一个成员）的抗体进行免疫组织化学研究。我们发现FAPα在正常人肺组织或有小叶中心型肺气肿证据的组织中不表达，但在所有IPF患者中均被诱导表达，其模式与主要在增生性肺泡上皮上发现的CD26不同。具体而言，FAPα在成纤维细胞灶和纤维化间质中被检测到，而在相邻结构正常的肺间质中未检测到。肺泡/气道上皮和血管平滑肌不表达FAPα。这是关于FAPα在IPF中表达的首次报道，我们的结果表明FAPα在纤维化灶中被选择性诱导，但在正常或肺气肿肺中不被诱导。未来研究将探讨FAPα是否可作为IPF疾病活动的标志物。
