Prevention of ischemia-reperfusion lung injury by sulfated Lewis(a) pentasaccharide. The Paris-Sud University Lung Transplantation Group.
Inhibition of polymorphonuclear neutrophil (PMN) adhesion to the pulmonary endothelium attenuates ischemia-reperfusion (I/R) lung injury. We hypothesized that 3'-sulfated Lewis(a) (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 (K(fc)), 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 microg) 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 K(fc), 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.
Reignier
J
J
Laboratoire de Chirurgie Expérimentale, Centre Chirurgical Marie Lannelongue, Université de Paris Sud, Le Plessis Robinson, France.
Sellak
H
H
Lemoine
R
R
Lubineau
A
A
Mazmanian
G M
GM
Detruit
H
H
Chapelier
A
A
Hervé
P
P
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007983:Lewis Blood Group Antigens; D055370:Lung Injury; D008297:Male; D008833:Microcirculation / Q000502:physiology; D009504:Neutrophils / Q000502:physiology*; D009844:Oligosaccharides / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D011247:Pregnancy; D011669:Pulmonary Wedge Pressure / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D014471:Umbilical Veins / Q000166:cytology / Q000201:enzymology
D007202:Indicators and Reagents; D007983:Lewis Blood Group Antigens; D009844:Oligosaccharides; D009195:Peroxidase