Anderson Clark L, Chaudhury Chaity, Kim Jonghan, Bronson C L, Wani Manzoor A, Mohanty Sudhasri
Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA.
Trends Immunol. 2006 Jul;27(7):343-8. doi: 10.1016/j.it.2006.05.004. Epub 2006 May 30.
Recent evidence validates a forgotten 40-year-old hypothesis: the MHC-related Fc receptor for IgG (FcRn) protects albumin from intracellular catabolic degradation, as it does for IgG, accounting for the uniquely long half-lives of both molecules and explaining their direct concentration-catabolism relationships. Albumin and IgG bind to FcRn at low pH but not at physiological pH. These two ligands bind independently of one another by distinctive mechanisms and to different surfaces of the receptor. Kinetic studies of FcRn-deficient mice indicate that, at steady-state, FcRn salvages from the degradative pathway a similar amount of albumin as is produced by mice and almost four-times more IgG than is produced. Thirty-fivefold more albumin than IgG molecules are protected from degradation by FcRn per unit time. It can be inferred that FcRn is expressed in nearly all cells. This receptor, originally described as transporting IgG from the mother to the fetus or neonate, now has a wider role central to the homeostatic regulation and conservation of both albumin and IgG throughout life.
近期证据证实了一个被遗忘40年的假说：与主要组织相容性复合体（MHC）相关的IgG Fc受体（FcRn）如同保护IgG一样，可保护白蛋白免于细胞内分解代谢降解，这解释了这两种分子独特的长半衰期，并说明了它们直接的浓度-分解代谢关系。白蛋白和IgG在低pH值下与FcRn结合，但在生理pH值下不结合。这两种配体通过独特机制彼此独立结合至受体的不同表面。对FcRn缺陷型小鼠的动力学研究表明，在稳态下，FcRn从降解途径挽救的白蛋白量与小鼠产生的白蛋白量相似，挽救的IgG量几乎是小鼠产生量的四倍。每单位时间内，被FcRn保护免于降解的白蛋白分子数量是IgG分子数量的35倍。可以推断，FcRn在几乎所有细胞中均有表达。这种受体最初被描述为将IgG从母体转运至胎儿或新生儿，现在在白蛋白和IgG终身稳态调节与保存方面发挥着更广泛的核心作用。
