TGF-BETA(1) CAUSES INCREASED ENDOTHELIAL ICAM-1 EXPRESSION AND LUNG INJURY

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 growt h factor-beta(1) (TGF-beta(1)) on the expression of ICAM-1 in human um bilical vein endothelial cells (HUVEC). TGF-beta(1) (1 ng/ml) increase d ICAM-1 and ICAM-1 mRNA expression in HUVEC, as assessed by flow cyto metry and Northern blot analysis, respectively. In addition, we invest igated whether exogenous recombinant TGF-beta(1) can cause neutrophil- mediated lung injury in guinea pigs. The plasma half-life of I-125-lab eled TGF-beta(1) in guinea pigs was 4.6 +/- 0.1 min, and the I-125 act ivity 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 neu trophils in BAL fluid, and numbers of neutrophils per alveolus in fixe d 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 th e control group. These results suggest that TGF-beta(1) causes neutrop hil-mediated lung injury, possibly through upregulation of ICAM-1 on e ndothelial cells, and might be important in the pathogenesis of lung i njury.