PREVENTION OF ISCHEMIA-REPERFUSION LUNG INJURY BY SULFATED LEWIS(A) PENTASACCHARIDE

Inhibition of polymorphonuclear neutrophil (PMN) adhesion to the pulmo nary endothelium attenuates ischemia-reperfusion (I/R) lung injury. We hypothesized that 3'-sulfated Lewis(a) (SuLa), a potent ligand for th e selectin adhesion molecules, may have a beneficial effect on I/R lun g injury, as measured by the filtration coefficient (K-fc), and reduce pulmonary sequestration of PMN as assessed by the lung myeloperoxidas e (MPO) activity. Blood-perfused rat lungs were subjected to 30 min of perfusion, 60 min of warm ischemia, and 90 min of reperfusion after t reatment with either SuLa (200 mu g) or saline. Effects of SuLa on PMN adhesion to cultured human umbilical vein endothelial cells (HUVEC) s timulated 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-induce d lung injury and PMN accumulation in lung. This protective effect mig ht be related to inhibition of PMN adhesion to endothelial cells.