TGF-BETA(1) CAUSES INCREASED ENDOTHELIAL ICAM-1 EXPRESSION AND LUNG INJURY
TGF-BETA(1) CAUSES INCREASED ENDOTHELIAL ICAM-1 EXPRESSION AND LUNG INJURY
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DOI：
10.1152/jappl.1994.77.3.1281
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发表时间：
1994-09-01
影响因子：
3.3
通讯作者：
RAFFIN, TA
中科院分区：
文献类型：
--
作者：
SUZUKI, Y;TANIGAKI, T;RAFFIN, TA
中性粒细胞对血管内皮的粘附部分由内皮细胞上的粘附分子介导，包括细胞内粘附分子 1 (ICAM-1)。我们检测了转化生长因子-β(1) (TGF-β(1)) 对人脐静脉内皮细胞 (HUVEC) 中 ICAM-1 表达的影响。通过流式细胞术和 Northern 印迹分析分别评估，TGF-β(1) (1 ng/ml) 增加了 HUVEC 中 ICAM-1 和 ICAM-1 mRNA 的表达。此外，我们还研究了外源重组TGF-β(1)是否会引起豚鼠中性粒细胞介导的肺损伤。 I-125 标记的 TGF-β(1) 在豚鼠体内的血浆半衰期为 4.6 +/- 0.1 分钟，注射后 8 小时 I-125 活性为 2.8 +/- 0.2%。与对照组相比，接受高剂量 TGF-β(1)（静脉注射 25 μg，然后 2 μg/h，持续 8 小时）的豚鼠的肺组织和支气管肺泡灌洗 (BAL) 液中 I-125 标记的白蛋白浓度与血浆中的 I-125 标记白蛋白浓度之比、肺湿重与干重比、BAL 液中的中性粒细胞数量以及固定肺切片中每个肺泡的中性粒细胞数量均有所增加。对照组。这些结果表明，TGF-β(1) 可能通过上调内皮细胞上的 ICAM-1 引起中性粒细胞介导的肺损伤，并且可能在肺损伤的发病机制中发挥重要作用。
Neutrophil adherence to vascular endothelium is partially mediated by adhesion molecules, including intracellular adhesion molecule 1 (ICAM-1), on endothelial cells. We examined the effect of transforming growth factor-beta(1) (TGF-beta(1)) on the expression of ICAM-1 in human umbilical vein endothelial cells (HUVEC). TGF-beta(1) (1 ng/ml) increased ICAM-1 and ICAM-1 mRNA expression in HUVEC, as assessed by flow cytometry and Northern blot analysis, respectively. In addition, we investigated whether exogenous recombinant TGF-beta(1) can cause neutrophil-mediated lung injury in guinea pigs. The plasma half-life of I-125-labeled TGF-beta(1) in guinea pigs was 4.6 +/- 0.1 min, and the I-125 activity was 2.8 +/- 0.2% 8 h after injection. The ratio of I-125-labeled albumin concentration in lung tissue and bronchoalveolar lavage (BAL) fluid to that in plasma, lung wet-to-dry weight ratio, numbers of neutrophils in BAL fluid, and numbers of neutrophils per alveolus in fixed lung sections increased in guinea pigs that received a high dose of TGF-beta(1) (25 mu g iv followed by 2 mu g/h for 8 h) compared with the control group. These results suggest that TGF-beta(1) causes neutrophil-mediated lung injury, possibly through upregulation of ICAM-1 on endothelial cells, and might be important in the pathogenesis of lung injury.