Fabriek Babs O, Møller Holger J, Vloet Rianka P M, van Winsen Lisa M, Hanemaaijer Roeland, Teunissen Charlotte E, Uitdehaag Bernard M J, van den Berg Timo K, Dijkstra Christine D
Department of Molecular Cell Biology and Immunology, VU Medical Center, The Netherlands.
J Neuroimmunol. 2007 Jul;187(1-2):179-86. doi: 10.1016/j.jneuroim.2007.04.016. Epub 2007 May 29.
The scavenger receptor CD163 is selectively expressed on tissue macrophages and human monocytes. CD163 has been implicated to play a role in the clearance of hemoglobin and in the regulation of cytokine production by macrophages. Membrane CD163 can be cleaved by matrix metalloproteinases (MMP) resulting in soluble CD163 (sCD163). In the present report the shedding of CD163 was investigated in multiple sclerosis (MS). An upregulation of plasma sCD163 and a down regulation of membrane CD163 in MS patients compared to healthy controls was observed. The levels of plasma sCD163 correlated with plasma MMP-9 levels in controls, but not in MS patients. Moreover, evidence was obtained for CD163-cleaving MMP activity in plasma of MS patients. Finally, the increased proteolytic shedding of CD163 correlated to reduced plasma levels of circulating inflammatory cytokines. Collectively, our results provide evidence for proteolytic shedding of CD163 in MS and suggest a possible link to cytokine production.
清道夫受体CD163在组织巨噬细胞和人类单核细胞上选择性表达。CD163被认为在血红蛋白清除以及巨噬细胞细胞因子产生的调节中发挥作用。膜型CD163可被基质金属蛋白酶(MMP)切割,产生可溶性CD163(sCD163)。在本报告中,对多发性硬化症(MS)中CD163的脱落进行了研究。与健康对照相比,观察到MS患者血浆sCD163上调,膜型CD163下调。在对照中,血浆sCD163水平与血浆MMP-9水平相关,但在MS患者中不相关。此外,还获得了MS患者血浆中具有切割CD163活性的MMP的证据。最后,CD163蛋白水解性脱落增加与循环炎症细胞因子血浆水平降低相关。总体而言,我们的结果为MS中CD163的蛋白水解性脱落提供了证据,并提示其与细胞因子产生可能存在联系。