Weaver Lehn K, Hintz-Goldstein Katharine A, Pioli Patricia A, Wardwell Kathleen, Qureshi Nilofer, Vogel Stefanie N, Guyre Paul M
Department of Physiology, Dartmouth Medical School, 1 Medical Center Drive, Lebanon, NH 03756, USA.
J Leukoc Biol. 2006 Jul;80(1):26-35. doi: 10.1189/jlb.1205756.
The hemoglobin scavenger receptor (HbSR) CD163 is a monocyte/macrophage-specific glycoprotein that binds and facilitates uptake of haptoglobin-hemoglobin (Hp-Hb) complexes, which are rapidly formed in the circulation upon hemolysis of red blood cells. Hemolysis can be caused by a diverse range of infectious agents and provides pathogens a source of iron to enhance their survival and replication. Previous work demonstrated that lipopolysaccharide (LPS) activates monocytes to cleave cell-bound HbSR into a soluble mediator that retains the capacity to bind Hp-Hb complexes. We report that blocking LPS activation of Toll-like receptor 4 prevents LPS-mediated shedding of CD163. Furthermore, activation of two other cell surface Toll-like receptors (TLR), TLR2 and TLR5, induces shedding of the HbSR from human monocytes. In contrast, treatment of monocytes with intracellular TLR3, TLR7, and TLR9 agonists failed to cause HbSR shedding, suggesting that this shedding event is selective to cell surface TLR activation. These data demonstrate that the soluble HbSR is released from monocytic cells in response to TLR signaling as an acute innate immune response to extracellular pathogen infections.
血红蛋白清除受体（HbSR）CD163是一种单核细胞/巨噬细胞特异性糖蛋白，它能结合并促进触珠蛋白-血红蛋白（Hp-Hb）复合物的摄取，这种复合物在红细胞溶血后于循环中迅速形成。溶血可由多种感染因子引起，并为病原体提供铁源以增强其存活和复制能力。先前的研究表明，脂多糖（LPS）可激活单核细胞，使其将细胞表面结合的HbSR裂解为一种可溶性介质，该介质仍保留结合Hp-Hb复合物的能力。我们报告称，阻断Toll样受体4的LPS激活可防止LPS介导的CD163脱落。此外，另外两种细胞表面Toll样受体（TLR），即TLR2和TLR5的激活，可诱导人单核细胞表面的HbSR脱落。相比之下，用细胞内TLR3、TLR7和TLR9激动剂处理单核细胞未能导致HbSR脱落，这表明这种脱落事件对细胞表面TLR激活具有选择性。这些数据表明，可溶性HbSR作为对细胞外病原体感染的急性固有免疫反应，是响应TLR信号从单核细胞中释放出来的。
