Kuwano K, Miyazaki H, Hagimoto N, Kawasaki M, Fujita M, Kunitake R, Kaneko Y, Hara N
Research Institute for Diseases of the Chest, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Am J Respir Cell Mol Biol. 1999 Jan;20(1):53-60. doi: 10.1165/ajrcmb.20.1.2941.
Pulmonary fibrosis begins with alveolitis, which progresses to destruction of lung tissue and excess collagen deposition. This process could be the result of DNA damage and a form of apoptosis. Therefore, we hypothesized that Fas ligand (FasL), which induces apoptosis in cells expressing Fas antigen (Fas), is associated with pulmonary fibrosis. We examined frozen lung tissues from seven patients with idiopathic pulmonary fibrosis (IPF), and bronchoalveolar lavage fluid (BALF) cells from 19 patients with IPF and from 17 patients with interstitial pneumonia associated with collagen vascular diseases (CVD-IP). We used five frozen lungs with normal lung parenchyma and BALF cells from 10 patients with solitary pulmonary nodule as controls. Reverse transcription-polymerase chain reaction (RT-PCR) showed that FasL messenger RNA (mRNA) was expressed in BALF cells from all patients with IPF and from 15 of 16 patients with CVD-IP. FasL mRNA was not detected in BALF cells except in one of 10 controls. RT in situ PCR detected FasL mRNA in inflammatory cells in BALF from patients with IPF. Immunohistochemistry detected FasL protein in infiltrating lymphocytes and granulocytes in all of seven frozen lung tissues of IPF, but in none of five control lung tissues. Additionally, the expression of Fas appeared to be upregulated in bronchiolar and alveolar epithelial cells in IPF compared with normal lung parenchyma by immunohistochemistry. We conclude that Fas and FasL were upregulated in fibrosing lung diseases and may associate with DNA damage or apoptosis of bronchiolar and alveolar epithelial cells in this disorder.
肺纤维化始于肺泡炎，随后发展为肺组织破坏和胶原过度沉积。这一过程可能是DNA损伤和一种凋亡形式的结果。因此，我们推测，在表达Fas抗原（Fas）的细胞中诱导凋亡的Fas配体（FasL）与肺纤维化有关。我们检查了7例特发性肺纤维化（IPF）患者的冷冻肺组织，以及19例IPF患者和17例与胶原血管疾病相关的间质性肺炎（CVD-IP）患者的支气管肺泡灌洗（BALF）细胞。我们使用5例肺实质正常的冷冻肺以及10例孤立性肺结节患者的BALF细胞作为对照。逆转录聚合酶链反应（RT-PCR）显示，所有IPF患者以及16例CVD-IP患者中的15例的BALF细胞中均表达FasL信使核糖核酸（mRNA）。除10例对照中的1例之外，在BALF细胞中未检测到FasL mRNA。RT原位PCR在IPF患者BALF的炎症细胞中检测到FasL mRNA。免疫组织化学在所有7例IPF冷冻肺组织的浸润淋巴细胞和粒细胞中检测到FasL蛋白，但在5例对照肺组织中均未检测到。此外，通过免疫组织化学发现，与正常肺实质相比，IPF细支气管和肺泡上皮细胞中Fas 的表达似乎上调。我们得出结论，在纤维化性肺疾病中Fas和FasL上调，并且可能与该疾病中细支气管和肺泡上皮细胞的DNA损伤或凋亡有关。
