Meningeal and perivascular macrophages of the central nervous system play a protective role during bacterial meningitis
Meningeal and perivascular macrophages of the central nervous system play a protective role during bacterial meningitis
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DOI：
10.4049/jimmunol.167.8.4644
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发表时间：
2001-10-15
影响因子：
4.4
通讯作者：
van den Berg, TK
中科院分区：
文献类型：
--
作者：
Polfliet, MMJ;Zwijnenburg, PJG;van den Berg, TK
脑膜（MM）和血管周围巨噬细胞（PVM）构成CNS中主要的常驻巨噬细胞群体，可与小胶质细胞区分开来。到目前为止，没有直接证据表明NIM和PVM在正常或病理条件下在CNS中可能发挥作用。为了阐明NIM和PVM在CNS炎症过程中的作用，我们开发了一种策略，使用单次脑室内注射甘露糖基化氯膦酸盐脂质体，这导致从CNS完全和选择性地消耗PVM和MM。实验性肺炎球菌脑膜炎期间MM和PVM的消耗导致疾病增加，这与脑脊液和血液中较高的细菌计数相关。这与白细胞流入脑脊液的减少有关，尽管相关趋化因子（例如，巨噬细胞炎症蛋白-2）和血管粘附分子的更高表达（例如，VCAM-1）。相反，较高的细菌计数与局部和全身炎症介质（例如，IL-6）表明局部白细胞和全身免疫激活增强，这可能解释了临床体征的恶化。这些发现表明PVM和MM在细菌性脑膜炎期间起保护作用，并表明这些巨噬细胞的主要作用是促进白细胞在血脑屏障处的流入。更一般地说，我们第一次证明了PVM和NIM在CNS炎症过程中起着至关重要的作用。
Meningeal (MM) and perivascular macrophages (PVM) constitute major populations of resident macrophages in the CNS that can be distinguished from microglial cells. So far, there is no direct evidence that demonstrates a possible role of NIM and PVM in the CNS during normal or pathologic conditions. To elucidate the role of the NIM and PVM during CNS inflammation, we have developed a strategy using a single intraventricular injection of mannosylated clodronate liposomes, which results in a complete and selective depletion of the PVM and MM from the CNS. Depletion of the MM and PVM during experimental pneumococcal meningitis resulted in increased illness, which correlated with higher bacteria counts in the cerebrospinal fluid and blood. This was associated with a decreased influx of leukocytes into the cerebrospinal fluid, which occurred despite an elevated production of relevant chemokines (e.g., macrophage-inflammatory protein-2) and a higher expression of vascular adhesion molecules (e.g., VCAM-1). In contrast, the higher bacterial counts correlated with elevated production of local and systemic inflammatory mediators (e.g., IL-6) indicating enhanced local leukocyte and systemic immune activation, and this may explain the worsening of the clinical signs. These findings show that the PVM and MM play a protective role during bacterial meningitis and suggest that a primary action of these macrophages is to facilitate the influx of leukocytes at the blood-brain barrier. More in general, we demonstrate for the first time that the PVM and NIM play a crucial role during inflammation in the CNS.