Grinnell B W, Hermann R B, Yan S B
Cardiovascular Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285-1543.
Glycobiology. 1994 Apr;4(2):221-5. doi: 10.1093/glycob/4.2.221.
The human anticoagulant factor, Protein C, is a plasma glycoprotein that has reported anti-ischaemic and anti-inflammatory properties. To explore potential mechanisms for these reported activities, we examined the effect of Protein C on the process of cell adhesion to vascular endothelial cells, which plays a critical role during inflammatory responses. We show that both human plasma-derived and human cell-produced recombinant Protein C inhibit E-selectin-mediated cell adhesion. This effect was not mediated through the serine protease activity of Protein C, but through its carbohydrates. Using oligosaccharides isolated from human cell-produced Protein C, we have defined a polylactosamine structural determinant that inhibits adhesion. This uncharged determinant appears to be a more potent ligand for E-selectin than the sialylated Lewis X antigen. Our data suggest a potential mechanism for the reported anti-inflammatory effects of Protein C and describe a new ligand for selectin-mediated adhesion.
人类抗凝血因子蛋白C是一种血浆糖蛋白，据报道具有抗缺血和抗炎特性。为了探究这些报道活性的潜在机制，我们研究了蛋白C对细胞与血管内皮细胞黏附过程的影响，该过程在炎症反应中起关键作用。我们发现，源自人血浆和人细胞产生的重组蛋白C均能抑制E-选择素介导的细胞黏附。这种作用不是通过蛋白C的丝氨酸蛋白酶活性介导的，而是通过其碳水化合物介导的。利用从人细胞产生的蛋白C中分离出的寡糖，我们确定了一种抑制黏附的多乳糖胺结构决定簇。这种不带电荷的决定簇似乎是比唾液酸化Lewis X抗原更强效的E-选择素配体。我们的数据提示了蛋白C报道的抗炎作用的潜在机制，并描述了一种选择素介导黏附的新配体。
