期刊
HUMAN PATHOLOGY
卷 37, 期 3, 页码 352-360出版社
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.humpath.2005.11.020
关键词
fibroblast; serine endopeptidase; FAP-alpha; CD26; idiopathic pulmonary fibrosis
类别
资金
- NHLBI NIH HHS [P50-HL67663] Funding Source: Medline
Fibroblast activation protein (FAP alpha) is a member of the cell Surface dipeptidyl peptidase (DPP) family of serine proteases. In its dimer form, FAP alpha exhibits gelatinase, collagenase, and DPP activity in vitro. Reactive fibroblasts in healing wounds and stromal fibroblasts associated with epithelial tumors express FAP alpha. 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 FAP alpha expression is induced in liver cirrhosis, with an expression pattern distinct from alpha-smooth muscle actin (alpha-SMA). In this study, we determine whether FAP alpha expression is selectively induced in areas of ongoing tissue remodeling characterized by fibroblast foci in IPF. Human lung tissue was obtained front patients with IPF, centrilobular emphysema, and normal lung. Immunohistochemical studies were performed using anti-FAP alpha antibody and antibodies against alpha-SMA and CD26 (DPPIV), another member of the DPP family. We found that FAP alpha 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 front that of CD26 found primarily on hyperplastic alveolar epithelium. Specifically, FAP alpha 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 FAP alpha. This is the first report of FAP alpha expression in IPF and our results Suggest that FAN is selectively induced in fibrotic foci, but not in normal or emphysematous lung. Future studies will address whether FAP alpha may be used as a marker for disease activity in IPF. (c) 2006 Elsevier Inc. All rights reserved.
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