CD163-positive perivascular macrophages in the human CNS express molecules for antigen recognition and presentation
CD163-positive perivascular macrophages in the human CNS express molecules for antigen recognition and presentation
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DOI：
10.1002/glia.20208
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发表时间：
2005-09-01
期刊：
影响因子：
6.2
通讯作者：
Dijkstra, CD
中科院分区：
文献类型：
--
作者：
Fabriek, BO;Van Haastert, ES;Dijkstra, CD
血管周围巨噬细胞 (PVM) 是中枢神经系统 (CNS) 中常驻巨噬细胞的一个亚群，由于其在血脑屏障的战略位置，可能在健康和疾病中发挥多种重要功能。功能证据表明，PVM 在啮齿动物实验性自身免疫性脑脊髓炎期间发挥支持作用。然而，PVM 在人类 CNS 中的功能仍然知之甚少。我们首先着手研究识别人 CD163 的抗体 EDhu1 特异性识别人 PVM 的有效性。其次，我们希望深入了解 PVM 在抗原识别和呈递中的功能，因此我们研究了 PVM 在正常和发炎的人类中枢神经系统（多发性硬化症 (MS) 脑损伤）中的 DC-SIGN、甘露糖受体、MHC II 类和几种共刺激分子的表达。使用常规免疫组织化学和双标记免疫荧光技术。我们发现 CD163 特异性地揭示了正常人中枢神经系统中的 PVM。在 MS 病变中，除了 PVM 染色量上调外，CD163 染色还显示泡沫巨噬细胞和小胶质细胞的表达。相反，在正常和发炎的脑组织中，甘露糖受体的表达仅限于 PVM。此外，我们发现人脑中的 PVM 亚群表达几种参与抗原识别、呈递和共刺激的分子。因此，PVM 在 BBB 中占据重要位置，能够识别抗原并将其呈递给 T 细胞，从而在调节人类中枢神经系统血管周围炎症中发挥作用。 (C) 2005 Wiley-Liss, Inc.
Perivascular macrophages (PVM) constitute a subpopulation of resident macrophages in the central nervous system (CNS) that by virtue of their strategic location at the blood-brain barrier potentially lend themselves to a variety of important functions in both health and disease. Functional evidence suggests that PVM play a supportive role during experimental autoimmune encephalomyelitis in rodents. However, the function of PVM in the human CNS remains poorly characterized. We first set out to investigate the validity of the antibody EDhu1, which recognizes human CD163, to specifically identify human PVM. Second, we wanted to gain insight into the function of PVM in antigen recognition and presentation and therefore we studied the expression of DC-SIGN, mannose receptor, MHC class II, and several costimulatory molecules by PVM in the normal and inflamed human CNS (multiple sclerosis (MS) brain lesions). Conventional immunohistochemistry and double-labeled immunofluoreseence techniques were used. We show that CD163 specifically reveals PVM in the normal human CNS. In MS lesions, CD163 staining reveals expression on foamy macrophages and microglia, besides an upregulation of the amount of PVM stained. In contrast mannose receptor expression is restricted to PVM in both normal and inflamed brain tissue. Furthermore, we show that a subpopulation of PVM in the human brain express several molecules involved in antigen recognition, presentation, and costimulation. Therefore PVM, which occupy a strategic location at the BBB, are equipped to recognize antigen and present it to T cells, supporting a role in the regulation of perivascular inflammation in the human CNS. (C) 2005 Wiley-Liss, Inc.