DiCorleto P E, de la Motte C A
Department of Vascular Cell Biology and Atherosclerosis Research, Cleveland Clinic Foundation, OH 44195.
J Immunol. 1989 Dec 1;143(11):3666-72.
Monocyte adhesion to endothelium represents the first step in the emigration of this leukocyte from blood to tissue during such pathologic and physiologic processes as atherosclerotic plaque development, wound healing, and inflammation. We have examined the role of carbohydrate moieties in the binding of mononuclear cells to endothelium in vitro. Wheat germ agglutinin (WGA) completely inhibited binding of the human monocytic cell line U937 to pig or human endothelial cells (EC). The inhibition was abolished by the presence of N-acetyl glucosamine, a preferred ligand for WGA. This sugar itself, however, had no effect on monocytic cell binding to EC, suggesting that WGA is inhibiting the cell-cell interaction by binding to a distinct sugar moiety. We tested a series of simple and phosphorylated sugars for the ability to inhibit U937 cell binding to EC. Two phosphorylated disaccharides, lactose-1-phosphate and maltose-1-phosphate, but not 14 other sugars, caused complete suppression of monocyte adhesion to EC. Among the inactive sugars were mannose-6-phosphate and fructose-1-phosphate, which have been shown by others to markedly suppress lymphocyte adhesion to EC. A nonionic detergent, n-octyl-beta-D-glucopyranoside (octyl glucoside), which contains a sugar group as a hydrophilic moiety, also inhibited U937 cell or human monocyte binding to human or porcine EC. The inhibition was observed at a nontoxic concentration of octyl glucoside and appeared to be due to an effect on the monocytic cell rather than the EC. When suboptimal doses of WGA and octyl glucoside were added in combination to the U937 cell-EC adhesion assay, the level of inhibition was greatly reduced when compared with either of the inhibitors alone, suggesting an interaction between these two blocking agents. Lactose-1-phosphate, but not octyl glucoside or WGA, blocked neutrophil adhesion to EC. In summary, our results indicate that specific cell surface carbohydrate groups are required for the adhesion of monocytes to the endothelium.
在动脉粥样硬化斑块形成、伤口愈合和炎症等病理和生理过程中，单核细胞与内皮细胞的黏附是这种白细胞从血液迁移到组织的第一步。我们已经在体外研究了碳水化合物部分在单核细胞与内皮细胞结合中的作用。麦胚凝集素（WGA）完全抑制了人单核细胞系U937与猪或人内皮细胞（EC）的结合。WGA的首选配体N-乙酰葡糖胺的存在消除了这种抑制作用。然而，这种糖本身对单核细胞与内皮细胞的结合没有影响，这表明WGA是通过与一个独特的糖部分结合来抑制细胞间相互作用的。我们测试了一系列简单糖和磷酸化糖抑制U937细胞与内皮细胞结合的能力。两种磷酸化二糖，乳糖-1-磷酸和麦芽糖-1-磷酸，但其他14种糖没有，导致单核细胞与内皮细胞的黏附完全受到抑制。在无活性的糖中包括甘露糖-6-磷酸和果糖-1-磷酸，其他人已表明它们能显著抑制淋巴细胞与内皮细胞的黏附。一种含有糖基团作为亲水部分的非离子洗涤剂正辛基-β-D-吡喃葡萄糖苷（辛基葡萄糖苷）也抑制U937细胞或人单核细胞与人和猪内皮细胞的结合。在辛基葡萄糖苷的无毒浓度下观察到了这种抑制作用，并且似乎是由于对单核细胞而不是内皮细胞的作用。当将次优剂量的WGA和辛基葡萄糖苷联合添加到U937细胞与内皮细胞的黏附试验中时，与单独使用任何一种抑制剂相比，抑制水平大大降低，这表明这两种阻断剂之间存在相互作用。乳糖-1-磷酸，但不是辛基葡萄糖苷或WGA，阻断了中性粒细胞与内皮细胞的黏附。总之，我们的结果表明单核细胞与内皮细胞的黏附需要特定的细胞表面碳水化合物基团。
