Prieels J P, Pizzo S V, Glasgow L R, Paulson J C, Hill R L
Proc Natl Acad Sci U S A. 1978 May;75(5):2215-9. doi: 10.1073/pnas.75.5.2215.
Evidence is presented suggesting that hepatocytes contain a receptor that binds glycoproteins specifically through fucose in alpha1-->3 linkage to N-acetylglucosamine. Human lactoferrin, which contains this type of linkage, is rapidly cleared from the circulation of mice after intravenous injection, and greater than 90% of the injected material is found in hepatocytes. Binding of lactoferrin is mediated through its carbohydrate groups, since its clearance is prolonged after periodate oxidation or after its oligosaccharide groups are extensively degraded with glycosidases. In addition, glycopeptides from lactoferrin inhibit lactoferrin clearance. That lactoferrin clearance is mediated through binding to its fucosyl groups is suggested for several reasons. First, transferrin and asialotransferrin, whose oligosaccharide groups are essentially structurally identical to those of lactoferrin but devoid of fucose, are not cleared on intravenous injection. Second, when fucose is incorporated into asialotransferrin by alpha1-->3 N-acetylglucosamine fucosyl transferase, the resulting fucosylated derivative is cleared rapidly. Neither mannan nor derivatives of orosomucoid that are cleared by binding to receptors for galactose, N-acetylglucosamine, or mannose, inhibit clearance of lactoferrin although clearance is inhibited by fucoidin. Finally, glycoproteins containing fucose in alpha1 --> 2 linkage to galactose or alpha1 --> 6 linkage to N-acetylglucosamine do not inhibit lactoferrin clerance by the liver. Since clearance of other glycoproteins, such as human lactoperoxidase, also appears to be mediated through binding to the same hepatocyte receptor as lactoferrin, it is concluded that the fucose-specific receptor studied here may fulfill other functions than binding lactoferrin. Preliminary studies with liver homogenates and detergent extracts of liver show binding in vitro.
有证据表明，肝细胞含有一种受体，该受体可通过α1→3连接至N - 乙酰葡糖胺上的岩藻糖特异性结合糖蛋白。人乳铁蛋白含有这种连接类型，静脉注射后能迅速从小鼠循环中清除，且超过90%的注射物质存在于肝细胞中。乳铁蛋白的结合是通过其碳水化合物基团介导的，因为在高碘酸盐氧化后或其寡糖基团被糖苷酶广泛降解后，其清除过程会延长。此外，乳铁蛋白的糖肽可抑制乳铁蛋白的清除。乳铁蛋白的清除是通过与岩藻糖基结合介导的，这一推测有以下几个原因。首先，转铁蛋白和去唾液酸转铁蛋白，其寡糖基团在结构上与乳铁蛋白基本相同但不含岩藻糖，静脉注射后不会被清除。其次，当岩藻糖通过α1→3 N - 乙酰葡糖胺岩藻糖基转移酶掺入去唾液酸转铁蛋白中时，所得的岩藻糖基化衍生物会迅速被清除。甘露聚糖以及通过与半乳糖、N - 乙酰葡糖胺或甘露糖受体结合而被清除的类黏液素衍生物，均不抑制乳铁蛋白的清除，尽管岩藻依聚糖可抑制清除。最后，含有α1→2连接至半乳糖或α1→6连接至N - 乙酰葡糖胺的岩藻糖的糖蛋白不会抑制肝脏对乳铁蛋白的清除。由于其他糖蛋白如人乳过氧化物酶的清除似乎也通过与乳铁蛋白相同的肝细胞受体结合介导，因此可以得出结论，此处研究的岩藻糖特异性受体可能具有除结合乳铁蛋白之外的其他功能。对肝脏匀浆和肝脏去污剂提取物的初步研究显示了体外结合情况。
