Birgens H S
Department of Hematology L, Herlev Hospital, University of Copenhagen, Denmark.
Adv Exp Med Biol. 1994;357:99-109. doi: 10.1007/978-1-4615-2548-6_10.
Several studies suggest biological functions of the iron-binding neutrophilic glycoprotein lactoferrin that imply an initial interaction with cells from the monocyte/macrophage family. Among these, an important role of lactoferrin as responsible for the inflammatory-induced blood hyposideremia and accumulation of iron in the monocyte/macrophage system has been suggested mainly based on experiments in rodents. In a series of experiments we have examined the binding of human lactoferrin to human monocytes. We have demonstrated the presence of a receptor binding including a high-affinity component and a low-affinity component. The affinity of the binding is compatible with a biological significance of this receptor (KD is about 10(-8) M, and the number of receptors about 10(6) per cell). More than 90% of the lactoferrin will dissociate from the cell. The binding is not truly reversible since lactoferrin will lose its receptor-binding property after dissociation from the cell. The only observed change in the molecule is a small decrease in isoelectric point from 8.9 to 8.8. Lactoferrin is able to translocate at least 50% of its bound iron to intracellular ferritin in monocytes. These findings are compatible with the idea that lactoferrin might be involved in the pathogenesis of the disturbances in iron metabolism observed during inflammation.
多项研究表明，铁结合性嗜中性糖蛋白乳铁蛋白具有生物学功能，这意味着它与单核细胞/巨噬细胞家族的细胞存在初始相互作用。其中，乳铁蛋白在炎症诱导的血液低铁血症以及单核细胞/巨噬细胞系统中铁蓄积方面发挥重要作用，这一观点主要基于啮齿动物实验提出。在一系列实验中，我们研究了人乳铁蛋白与人单核细胞的结合情况。我们证实存在一种受体结合，包括一个高亲和力成分和一个低亲和力成分。这种结合的亲和力与该受体的生物学意义相符（解离常数约为10⁻⁸ M，每个细胞的受体数量约为10⁶）。超过90%的乳铁蛋白会从细胞上解离。这种结合并非真正可逆，因为乳铁蛋白从细胞解离后会失去其受体结合特性。分子中唯一观察到的变化是等电点从8.9略有下降至8.8。乳铁蛋白能够将其结合铁的至少50%转运至单核细胞内的铁蛋白中。这些发现与乳铁蛋白可能参与炎症期间观察到的铁代谢紊乱发病机制的观点相符。
