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| 1 | Endothelial cell-specific anticoagulation reduces inflammation in a mouse model of acute lung injury显示文摘Tissue factor (TF)-dependent coagulation contributes to lung inflammation and the pathogenesis of acute lung injury (ALI). In this study, we explored the roles of targeted endothelial anticoagulation in ALI using two strains of transgenic mice expressing either a membrane-tethered human tissue factor pathway inhibitor (hTFPI) or hirudin fusion protein on CD31^+ cells, including vascular endothelial cells (ECs). ALI was induced by intratracheal injection of LPS, and after 24 h the expression of TF and protease-activated receptors (PARs) on EC in lungs were assessed, alongside the extent of inflammation and injury. The expression of TF and PARs on the EC in lungs was upregulated after ALI. In the two strains of transgenic mice, expression of either of hTFPI or hirudin by EC was associated with significant reduction of inflammation, as assessed by the extent of leukocyte infiltration or the levels of proinflammatory cytokines, and promoted survival after LPS-induced ALI. The beneficial outcomes were associated with inhibition of the expression of chemokine CCL2 in lung tissues. The protection observed in the CD31-TFPI-transgenic strain was abolished by injection of an anti-hTFPI antibody, but not by prior engraftment of the transgenic strains with WT bone marrow, confirming that the changes observed were a specific transgenic expression of anticoagulants by EC. These results demonstrate that the inflammation in ALI is TF and thrombin dependent, and that expression of anticoagulants by EC significantly inhibits the development of ALI via repression of leukocyte infiltration, most likely via inhibition of chemokine gradients. These data enhance our understanding of the pathology of ALI and suggest a novel therapeutic strategy for treatment. | Jian Lou Yue Hu Min-dan Wu Luan-qing Che Yin-fang Wu Yun Zhao Bao-ping Tian Zheng-qiang Bao Chen Zhu Yan-ping Wu Lu-lu He Chun-xue Bai Jian Zhou Song-min Ying Wen Li Zhi-hua Chen Da-xin Chen Anthony Dorling Hua-hao Shen | 2019 | Acta Pharmacologica Sinica2019，40，6： | 7 |
| 2 | A Spectroscopic inestigation of swainsonine: anα-mannosidase inhibitor isolated from swaisona canescens显示文摘 | Colegate S M Dorling P R Huxtable C R | 1979 | Aust J Chem1979，32，： | 1 |
| 3 | Neona- tal disease severity scoring systems显示文摘 | DORLING J S FIELD D J MANKTELOW B | 2005 | Arch Dis Child Fetal Neonatal Ed2005，90，： | 1 |
| 4 | Life expectancy : women now on top everywhere显示文摘 | Barford A Dorling D Smith G | 2006 | BMJ2006，332，7545： | 1 |
| 5 | Neural network modelling and prediction of hourly NOx and NO2 concentrations in urban air in London显示文摘 | GARDNER M W DORLING S R | 1999 | Atmospheric Environment1999，，33： | 1 |
| 6 | Study of the biodegradation and in vivo biocompatibility of novel biomaterials 显示文摘 | Fulzele S V Satturwar P M Dorle A K | 2003 | European Journal of Pharmaceutical Sciences2003，20，1： | 1 |
| 7 | Poverty and Place in Britain, 1968 - 99 显示文摘 | Eldin Fahmy David Gordon Danny Dorling Janette Rigby Ben Wheeler | 2011 | Environment and Planning A2011，43，3： | 1 |
| 8 | A spectro- scopic investination of swainsonine : an a-mannosidase inhibitor isolated from Swainsina canecens显示文摘 | Colegate S M Dorling P R Huxtable C R | 1979 | Aust J Chem1979，32，： | 1 |
| 9 | Progenitor cells and vascular disease 显示文摘 | Jevon M Dorling A Hornick PI | 2008 | Cell Prolif2008，41，1： | 1 |
| 10 | A spectroscopic investigation of swainsonine:an α-mannosidase inhibitor isolated from swainsonina cancens显示文摘 | Colegate S M Dorling P R Huxtable C R | 1979 | Australia Journal Chemistry1979，32，： | 1 |
| 11 | A spectroscopic inestigation of swainsonine : an α-mannosidase inhibitor isolated from swainsona canescens 显示文摘 | Colegate S M Dorling P R Huxtable C R | 1979 | Aust J Chem1979，32，： | 1 |
| 12 | Artificial neural networks ( themultilayer perceptron)-a review of applications in the at-mospheric sciences 显示文摘 | Gardner M W Dorling S R | 1998 | Atmospheric environment1998，32，14： | 1 |
| 13 | Regulated endothelial cell expression of novel anticoagulants: a strategy for the prevention and therapy of intravascular thrombosis显示文摘 | Dorling A Chen D Riesbeck K | 2000 | Transplant Proc2000，32，5： | 1 |
| 14 | Artificial neural networks (the multilayer perceptron)-a review of applications in the atmospheric sciences显示文摘 | DORLING S R | 1998 | Atmospheric Environment1998，32，1415： | 1 |
| 15 | Modelling SO2 concentration at a point with statistical approaches显示文摘 | NUNNARI G DORLING S SCHLINK U | 2004 | Environmental Modelling & Software2004，，19： | 1 |
| 16 | Visibility trends in the UK 1950 - 1997 显示文摘 | DOYLE M DORLING S | 2002 | Atmospheric Environment2002，36，19： | 1 |
| 17 | A spectroscopic investigation of swainsonine : an a-mannosidase inhibitor isolated from Swainsina canecens显示文摘 | COLEGATE S M DORLING P R HUXTABLE C R | 1979 | Aust J Chem1979，32，： | 1 |
| 18 | Evalution of the activity of a post-operative analgesia department in Canadian hospital显示文摘 | Fugare F Dorle P Veillette Y | 1996 | Ann Fr Anesth Rev1996，15，： | 1 |
| 19 | Diabetes in old male offspring of rat dams fed a reduced protein diet 显示文摘 | Dorling MW Pawlak DB | 2001 | Int J Exp Diabetes Res2001，2，2： | 1 |
| 20 | 'One-pot' meth- ylation of Fmoc amino acids 显示文摘 | R W A Luke P G T Boyce E K Dorling | 1996 | Tetrahedron Lett1996，37，2： | 1 |
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