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 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 125I-labeled TGF-beta 1 in guinea pigs was 4.6 +/- 0.1 min, and the 125I activity was 2.8 +/- 0.2% 8 h after injection. The ratio of 125I-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 micrograms i.v. followed by 2 micrograms/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.
Department of Medicine, Stanford University Medical Center 94305.
Y
Y
Suzuki
T
T
Tanigaki
D
D
Heimer
W
W
Wang
W G
WG
Ross
G A
GA
Murphy
A
A
Sakai
H H
HH
Sussman
T H
TH
Vu
T A
TA
Raffin
D000818:Animals; D016207:Cytokines / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000276:immunology* / Q000473:pathology; D006168:Guinea Pigs; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology / Q000473:pathology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D008233:Lymphotoxin-alpha / Q000493:pharmacokinetics / Q000494:pharmacology*; D009504:Neutrophils / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D014471:Umbilical Veins
D016207:Cytokines; D016169:Lymphocyte Function-Associated Antigen-1; D008233:Lymphotoxin-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1