脑脊液
炎症
脑膜炎
小胶质细胞
免疫学
趋化因子
中枢神经系统
巨噬细胞
免疫系统
病理
生物
血脑屏障
医学
神经科学
体外
精神科
生物化学
作者
Machteld M. J. Polfliet,Petra J.G. Zwijnenburg,A. Marceline van Furth,Tom van der Poll,E. A. Döpp,C. Renardel De Lavalette,E M van Kesteren-Hendrikx,Nico van Rooijen,C.D. Dijkstra,Timo K. van den Berg
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2001-10-15
卷期号:167 (8): 4644-4650
被引量:127
标识
DOI:10.4049/jimmunol.167.8.4644
摘要
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 MM and PVM in the CNS during normal or pathologic conditions. To elucidate the role of the MM 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 MM play a crucial role during inflammation in the CNS.
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