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J Appl Physiol 82: 1058-1063, 1997;
8750-7587/97 $5.00
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Journal of Applied Physiology
Vol. 82, No. 4, pp. 1058-1063, April 1997
PULMONARY CIRCULATION AND LUNG FLUID BALANCE

Prevention of ischemia-reperfusion lung injury by sulfated Lewisa pentasaccharide

Jean Reignier, Hassan Sellak, Rémy Lemoine, André Lubineau, Guy Michel Mazmanian, Hélène Detruit, Alain Chapelier, Philippe Hervé, and The Paris-Sud University Lung Transplantation Group

Laboratoire de Chirurgie Expérimentale, Jeune Equipe 324, Centre Chirurgical Marie Lannelongue, Université de Paris Sud, Le Plessis Robinson 92350; and Laboratoire de Chimie Organique et Multifonctionelle, Université de Paris Sud, Orsay 91405, France

Received 15 March 1996; accepted in final form 25 November 1996.

Reignier, Jean, Hassan Sellak, Rémy Lemoine, André Lubineau, Guy Michel Mazmanian, Hélène Detruit, Alain Chapelier, Philippe Hervé, and The Paris-Sud University Lung Transplantation Group. Prevention of ischemia-reperfusion lung injury by sulfated Lewisa pentasaccharide. J. Appl. Physiol. 82(4): 1058-1063, 1997.---Inhibition of polymorphonuclear neutrophil (PMN) adhesion to the pulmonary endothelium attenuates ischemia-reperfusion (I/R) lung injury. We hypothesized that 3'-sulfated Lewisa (SuLa), a potent ligand for the selectin adhesion molecules, may have a beneficial effect on I/R lung injury, as measured by the filtration coefficient (Kfc), and reduce pulmonary sequestration of PMN as assessed by the lung myeloperoxidase (MPO) activity. Blood-perfused rat lungs were subjected to 30 min of perfusion, 60 min of warm ischemia, and 90 min of reperfusion after treatment with either SuLa (200 µg) or saline. Effects of SuLa on PMN adhesion to cultured human umbilical vein endothelial cells (HUVEC) stimulated with tumor necrosis factor-alpha and calcium ionophore were also investigated. Compared with preischemia conditions, I/R induced a significant increase in Kfc, which was attenuated with SuLa (80 ± 8 vs. 30 ± 5%; P < 0.001). SuLa reduced lung MPO and PMN adhesion to stimulated HUVEC. These results indicate that SuLa reduces I/R-induced lung injury and PMN accumulation in lung. This protective effect might be related to inhibition of PMN adhesion to endothelial cells.

endothelium; selectins; neutrophils; rat lung

0161-7567/97 $5.00 Copyright © 1997 the American Physiological Society




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