Miki H, Mio T, Nagai S, Hoshino Y, Nagao T, Kitaichi M, Izumi T
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Japan.
Am J Respir Crit Care Med. 2000 Dec;162(6):2259-64. doi: 10.1164/ajrccm.162.6.9812029.
The aim of this study was to compare the function of lung fibroblasts obtained from surgically biopsied specimens of patients with idiopathic pulmonary fibrosis/usual interstitial pneumonia (UIP; n = 5), nonspecific interstitial pneumonia (NSIP; n = 5), and normal parts of surgically resected lungs (control; n = 5). The results showed that (1) fibroblasts obtained from UIP showed increased contractility compared with those obtained from NSIP or controls (UIP, 72.7 +/- 6.21%; NSIP, 32.8 +/- 5.46; controls, 28.5 +/- 3.51, p < 0.01 in UIP versus NSIP or control); (2) this increase in contractility was consistent with enhanced F-actin content in fibroblasts; (3) conditioned media from UIP fibroblast cultures enhanced control fibroblast contractility, whereas those obtained from NSIP or controls did not; (4) the 180 and 25 kD products representing the contractility in conditioned media were identified as fibronectin (ED-A domain) and TGF-beta1 by immunoblots, respectively; (5) the UIP-conditioned media contained higher amounts of fibronectin or TGF-beta 1 (fibronectin: UIP 289 +/- 47.1 ng/ml, NSIP 121 +/- 23.0, control 118 +/- 16.0; TGF-beta1: UIP 798 +/- 119 pg/ml, NSIP 246 +/- 69.1, control 247 +/- 53.6, p < 0.01 in UIP versus NSIP or control); () the contractility positively correlated with the amount of either fibronectin (r = 0.867, p < 0.001, n = 15) or TGF-beta 1 (r = 0.939, p < 0.001, n = 15), respectively. Thus, UIP fibroblasts showed greater contractility than did NSIP fibroblasts and up-regulated control fibroblasts.
本研究旨在比较从特发性肺纤维化/普通间质性肺炎(UIP;n = 5)、非特异性间质性肺炎(NSIP;n = 5)患者的手术活检标本以及手术切除肺的正常部分(对照;n = 5)中获取的肺成纤维细胞的功能。结果显示:(1)与从NSIP或对照中获取的成纤维细胞相比,从UIP中获取的成纤维细胞收缩性增强(UIP为72.7 +/- 6.21%;NSIP为32.8 +/- 5.46;对照为28.5 +/- 3.51,UIP与NSIP或对照相比,p < 0.01);(2)这种收缩性的增加与成纤维细胞中F - 肌动蛋白含量的增加一致;(3)UIP成纤维细胞培养的条件培养基增强了对照成纤维细胞的收缩性,而从NSIP或对照中获取的条件培养基则没有;(4)通过免疫印迹法,条件培养基中代表收缩性的180和25 kD产物分别被鉴定为纤连蛋白(ED - A结构域)和转化生长因子 - β1;(5)UIP条件培养基中纤连蛋白或转化生长因子 - β1的含量更高(纤连蛋白:UIP为289 +/- 47.1 ng/ml,NSIP为121 +/- 23.0,对照为118 +/- 16.0;转化生长因子 - β1:UIP为798 +/- 119 pg/ml,NSIP为246 +/- 69.1,对照为247 +/- 53.6,UIP与NSIP或对照相比p < 0.0;(6)收缩性分别与纤连蛋白量(r = 0.867,p < 0.001,n = 15)或转化生长因子 - β1量(r = 0.939,p < 0.001,n = 15)呈正相关。因此UIP成纤维细胞比NSIP成纤维细胞表现出更大的收缩性,并上调对照成纤维细胞的收缩性。