CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin
CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin
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DOI：
10.1182/blood-2005-03-1014
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发表时间：
2006-01-01
期刊：
影响因子：
20.3
通讯作者：
Schaffner, A
中科院分区：
文献类型：
--
作者：
Schaer, DJ;Schaer, CA;Schaffner, A
CD 163介导巨噬细胞对血红蛋白-触珠蛋白（Hb-Hp）复合物的内化。由于在严重溶血过程中Hp结合能力耗尽，推测存在Hp非依赖性Hb清除途径。我们证明，血红蛋白有效地相互作用与CD 163在没有Hp。不仅是血红蛋白内化到一个内体区室的CD 163作为一个积极的受体依赖性的内吞作用的结果，它也抑制Hb-Hp复合物的摄取，这表明一个共同的受体结合位点。游离血红蛋白进一步诱导血红素加氧酶mRNA在CD 163（+）HEK 293细胞中表达，但在CD 163（-）细胞中不诱导。通过证明CD 163介导α-DBBF交联Hb（一种形成最小Hp复合物的化学修饰Hb）的摄取，提供了Hp非依赖性Hb-CD 163相互作用的其他证据。此外，对Hb的某些修饰，如聚合或将特定官能团（3个赖氨酰残基）连接到β-Cys 93上，可以减少或增强这种摄取途径。在人巨噬细胞中，Hp-复合物的形成在低配体浓度（11 μ g/mL）下显著增强Hb摄取，但在高配体浓度（大于100 μ g/mL）下不显著增强Hb摄取，从而支持巨噬细胞Hb-清除的浓度依赖性双相模型。这些结果确定了CD 163作为天然血红蛋白和小分子量血红蛋白为基础的血液替代品的清道夫受体后，幽门螺杆菌耗尽。
CD163 mediates the internalization of hemoglobin-haptoglobin (Hb-Hp) complexes by macrophages. Because Hp binding capacity is exhausted during severe hemolysis, an Hp-independent Hb-clearance path. way is presumed to exist. We demonstrate that Hb interacts efficiently with CD163 in the absence of Hp. Not only is Hb internalized into an endosomal compartment by CD163 as a result of active receptor-dependent endocytosis; it also inhibits the uptake of Hb-Hp complexes, suggesting a common receptor-binding site. Free Hb further induces heme oxygenase mRNA expression in CD163(+) HEK293 cells, but not in CD163(-) cells. Additional evidence for Hp-independent Hb-CD163 interaction is provided by the demonstration that CD163 mediates the uptake of alpha alpha-DBBF crosslinked Hb, a chemically modified Hb that forms minimal Hp complexes. Moreover, certain modifications to Hb, such as polymerization or the attachment of specific functional groups (3 lysyl residues) to the beta-Cys93 can reduce or enhance this pathway of uptake. In human macrophages, Hp-complex formation critically enhances Hb uptake at low (11 mu g/mL), but not at high (greater than 100 mu g/mL), ligand concentrations, lending support for a concentration-dependent biphasic model of macrophage Hb-clearance. These results identify CD163 as a scavenger receptor for native Hb and small-molecular-weight Hb-based blood substitutes after Hp depletion.