Mulligan M S, Paulson J C, De Frees S, Zheng Z L, Lowe J B, Ward P A
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.
Nature. 1993 Jul 8;364(6433):149-51. doi: 10.1038/364149a0.
Neutrophil recruitment into tissues is a multistep process involving sequential engagement of adhesion molecules, including selectins (E,P,L), which are reactive with oligosaccharides, and the family of beta 2 integrins which are reactive with endothelial intercellular adhesion molecules. These processes result in the initial rolling of leukocytes along the endothelial surfaces, followed by the firm attachment of leukocytes to the endothelium. The intravenous infusion of cobra venom factor into rats results in acute lung injury that is neutrophil-dependent, oxygen radical mediated and P-selectin-dependent. Here we report that infusion of sialyl-Lewis X, a ligand for P-selectin, dramatically reduced lung injury and diminished the tissue accumulation of neutrophils, whereas irrelevant oligosaccharides had no such effects. These results suggest that sialyl-Lewis X carbohydrates may be used as a new strategy for anti-inflammatory therapy.
中性粒细胞募集到组织中是一个多步骤过程，涉及粘附分子的顺序参与，包括与寡糖反应的选择素（E、P、L）以及与内皮细胞间粘附分子反应的β2整合素家族。这些过程导致白细胞最初沿内皮表面滚动，随后白细胞牢固附着于内皮。向大鼠静脉输注眼镜蛇毒因子会导致急性肺损伤，该损伤依赖中性粒细胞、由氧自由基介导且依赖P-选择素。在此我们报告，输注P-选择素的配体唾液酸化路易斯X可显著减轻肺损伤并减少中性粒细胞在组织中的积聚，而无关的寡糖则无此作用。这些结果表明，唾液酸化路易斯X碳水化合物可能用作抗炎治疗的新策略。
