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DOI: 10.1055/s-2002-34578
© Georg Thieme Verlag Stuttgart · New York
A Novel Sialyl Lewisx Analogue Attenuates Ischemia Reperfusion Injury in Rabbit Lung
Publication History
Received October 18, 2001
Publication Date:
08 October 2002 (online)
Abstract
Background: We investigated the effects of OJ-R9545, a novel Sialyl Lewisx analogue, on lung ischemia-reperfusion (IR) injury using an in vivo rabbit model. Methods: The left hilum of the lung was clamped for 110 minutes; the lung was then reperfused for 90 minutes. Either OJ-R9545 (10 mg/kg) or vehicle solution was administered from 10 minutes before reperfusion to 60 minutes after reperfusion in the OJ-R (+) and OJ-R (-) group (n = 6 in each group), respectively. The sham group (n = 3) underwent an identical procedure without ischemia. Results: Arterial oxygen tensions in the OJ-R (+) group were superior to those in the OJ-R (-) group from 30 to 90 minutes after reperfusion (p < 0.05 and p < 0.01). Lung wet/dry weight ratio and myeloperoxidase activity after reperfusion in the OJ-R (+) group were both significantly lower than the corresponding figures in the OJ-R (-) group (p < 0.05). The intrapulmonary leukocytes were significantly reduced in the OJ-R (+) group compared with those in the OJ-R (-) group (p < 0.01). Conclusions: OJ-R9545 attenuates lung IR injury by preventing leukocyte infiltration into the lung.
Key words
Sialyl Lewisx analogue - Leukocyte infiltration - Lung ischemia reperfusion injury
References
- 1 Horgan M J, Ge M, Gu J, Rothlein R, Malik A B. Role of ICAM-1 in neutrophil-mediated lung vascular injury after occlusion and reperfusion. Am J Phhysiol. 1991; 261 H1578-H1584
- 2 Butcher E C. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell. 1991; 67 1033-1036
- 3 Lefer A M, Weyrich A S, Buerke M. Role of selectins, a new family of adhesion moleculres, in ischaemia-reperfusion injury. Cardiovasc Res. 1994; 28 289-294
- 4 Foxall C, Watson S R, Dowbenko D. et al . The three members of the selection receptor family recognize a common carbohydrate epitope, the sialyl Lewisx oligosaccharide. J CellBiol. 1992; 117 895-902
- 5 Mulligan M S, Paulson J C, De Frees S, Zheng Z L, Lowe J B, Ward P A. Protective effects of oligosaccharides in P-selectin-dependent lung injury. Nature . 1993; 364 149-151
- 6 Okubo K, Kosaka S, Isowa N. et al . Amelioration of ischemia-reperfusion injury by human thioredoxin in rabbit lung. J Thorac Cardiovasc Surg. 1997; 113 1-9
- 7 Kawashima M, Bando T, Nakamura T. et al . Cytoprotective effects ofnitroglycerin in ischemia-reperfusion-induced lung injury. Am J Respir Crit Care Med. 2000; 161 935-943
- 8 Lowry O H, Rosebrough N J, Fair A L, Randell R J. Protein measurement with the Folin Phenol reagent. J Biol Chem. 1951; 193 265-275
- 9 Lasky L A. Selectins: interpreters of cell-specific carbohydrate information during inflammation. Science. 1992; 258 964-969
- 10 Misawa K, Toledo-Pereyra L H, Phillips M L, Garcia-Cirado F J, Lopez-neblina F, Paez-Rollys A. Role of sialyl Lewisx in total hepatic ischemia and reperfusion. J Am Coll Surg. 1996; 182 251-256
- 11 Han K T, Sharar S R, Phillips M L, Harlan J M, Winn R K. Sialyl Lewisx oligosaccharide reduces ischemia-reperfusion injury in the rabbit ear. J Immunol. 1995; 155 4011-4015
- 12 Lefer D J, Flynn D M, Phillips M L, Ratcliffe M, Buda A J. A novel Sialyl Lewisx analog attenuates neutrophil accumulation and myocardial necrosis after ischemia and reperfusion. Circulation. 1994; 90 2390-2401
- 13 Buerke M, Weyrich A S, Zheng Z, Gaeta F C, Forrest M J, Lefer A M. Sialyl Lewisx-containing oligosaccharide attenuates myocardial reperfusion injury in cats. J Clin Invest. 1994; 93 1140-1148
- 14 Schmid R A, Yamashita M, Boasquevisque C H. et al . Carbohydrate selectin inhibitor CY-1503 reduces neutrophil migration and reperfusion injury in canine pulmonary allografts. J Heart Lung Transplant. 1997; 16 1054-1061
- 15 Brandt M, Boeke K, Phillips M L, Steinhoff G, Haverich A. Effect of oligosaccharides on rejection and reperfusion injury after lung transplantation. J Heart Lung Transplant. 1997; 16 352-359
- 16 Gill E A, Kong Y, Horwitz L D. An oligosaccharide sialyl-Lewisx analogue does not reduce myocardial infarct size after ischemia and reperfusion in dogs. Circulation. 1996; 94 542-546
- 17 Eppinger M J, Jones M L, Deeb G M, Bolling S F, Ward P A. Pattern of injury and the role of neutrophils in reperfusion injury of rat lung. J Surg Res. 1995; 58 713-718
- 18 Tofukuji M, Metais C, Collard C D. et al . Effect of Sialyl Lewisx oligosaccharide on myocardial and cerebral injury in the pig. Ann Thorac Surg. 1999; 67 1 112-119
Hiromi Wada MD
Department of Thoracic Surgery, Faculty of Medicine, Kyoto University
Shogoin kawahara-cho 54
Sakyo-ku o Kyoto 606-8507
Japan
Phone: + 81-75-751-3835
Fax: + 81-75-751-4647
Email: wadah@kuhp.kyoto-u.ac.jp