Kristiansen M, Graversen J H, Jacobsen C, Sonne O, Hoffman H J, Law S K, Moestrup S K
Department of Medical Biochemistry, University of Aarhus, Denmark.
Nature. 2001 Jan 11;409(6817):198-201. doi: 10.1038/35051594.
Intravascular haemolysis is a physiological phenomenon as well as a severe pathological complication when accelerated in various autoimmune, infectious (such as malaria) and inherited (such as sickle cell disease) disorders. Haemoglobin released into plasma is captured by the acute phase protein haptoglobin, which is depleted from plasma during elevated haemolysis. Here we report the identification of the acute phase-regulated and signal-inducing macrophage protein, CD163, as a receptor that scavenges haemoglobin by mediating endocytosis of haptoglobin-haemoglobin complexes. CD163 binds only haptoglobin and haemoglobin in complex, which indicates the exposure of a receptor-binding neoepitope. The receptor-ligand interaction is Ca2+-dependent and of high affinity. Complexes of haemoglobin and multimeric haptoglobin (the 2-2 phenotype) exhibit higher functional affinity for CD 163 than do complexes of haemoglobin and dimeric haptoglobin (the 1-1 phenotype). Specific CD163-mediated endocytosis of haptoglobin-haemoglobin complexes is measurable in cells transfected with CD163 complementary DNA and in CD163-expressing myelo-monocytic lymphoma cells.
血管内溶血既是一种生理现象，也是在各种自身免疫性、感染性（如疟疾）和遗传性（如镰状细胞病）疾病中加速时出现的严重病理并发症。释放到血浆中的血红蛋白被急性期蛋白触珠蛋白捕获，在溶血加剧时，触珠蛋白会从血浆中耗尽。在此，我们报告了急性期调节和信号诱导巨噬细胞蛋白CD163的鉴定，它是一种通过介导触珠蛋白-血红蛋白复合物的内吞作用来清除血红蛋白的受体。CD163仅结合处于复合物状态的触珠蛋白和血红蛋白，这表明存在一个受体结合新表位。受体-配体相互作用依赖于Ca2+且具有高亲和力。血红蛋白与多聚体触珠蛋白（2-2表型）的复合物对CD163的功能亲和力高于血红蛋白与二聚体触珠蛋白（1-1表型）的复合物。在用CD163互补DNA转染的细胞以及表达CD163的髓单核细胞淋巴瘤细胞中，可检测到触珠蛋白-血红蛋白复合物特异性的CD163介导的内吞作用。
