THE ACUTE INFLAMMATORY RESPONSE TO LIPOPOLYSACCHARIDE IN CNS PARENCHYMA DIFFERS FROM THAT IN OTHER BODY-TISSUES
THE ACUTE INFLAMMATORY RESPONSE TO LIPOPOLYSACCHARIDE IN CNS PARENCHYMA DIFFERS FROM THAT IN OTHER BODY-TISSUES
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DOI：
10.1016/0306-4522(92)90347-5
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发表时间：
1992-05-01
期刊：
影响因子：
3.3
通讯作者：
GORDON, S
中科院分区：
文献类型：
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作者：
ANDERSSON, PB;PERRY, VH;GORDON, S
急性炎症对于抵抗感染、伤口修复和介导自身免疫组织破坏是重要的。急性炎症中的骨髓单核细胞募集是对组织损伤的定型和非特异性反应，在2小时内开始。在这项研究中，将脂多糖注射到小鼠中枢神经系统和小鼠的其他身体部位，以比较炎症反应。剂量的脂多糖，诱导典型的骨髓单核细胞招募皮肤和脉络丛在中枢神经系统实质中没有影响，除了局部居民小胶质细胞的形态激活。CNS实质反应独立于脉络丛-脑室中的反应进行，并且具有三个不同且独特的阶段。最初有最小的中性粒细胞渗出和两天的延迟之前，任何巨噬细胞-小胶质细胞数量的增加。接下来，在第三天期间，巨噬细胞-小胶质细胞数量迅速增加，主要是由于血液单核细胞的募集。在此阶段，白细胞募集仅限于单核细胞，单核细胞迅速采用树枝状小胶质细胞表型。单核细胞迁移通过一个完整的血脑屏障独立的溶质渗透性的变化。最后，在脑内注射2 μ g脂多糖后一周，在白色物质中主要有鲜艳的骨髓单核细胞反应。此时，白细胞反应破坏血脑屏障，单核吞噬细胞表达巨噬细胞形态和丰富的主要组织相容性复合物II类抗原，并存在T淋巴细胞。髓单核细胞进入中枢神经系统被部分抑制的3型补体受体，已知介导白细胞粘附到内皮elsewhere.The过程中，导致其他组织中的快速招募髓单核细胞在中枢神经系统实质中是不存在的。了解负责的分子机制可能有相当大的意义，无论是中枢神经系统的病理生理学，以及可能的抗炎治疗应用在身体的其他地方。
Acute inflammation is important for defence against infection, wound repair and the mediation of auto-immune tissue destruction. Myelomonocytic recruitment in acute inflammation is a stereotyped and non-specific response to tissue insult which begins within 2 h. In this study, lipopolysaccharide was injected into the murine CNS and other body sites of mice to compare the inflammatory responses. Doses of lipopolysaccharide which induced typical myelomonocytic recruitment in skin and the choroid plexus had no effect in CNS parenchyma, apart from the morphological activation of local resident microglia. The CNS parenchymal response proceeded independently of that in the choroid plexus-cerebral ventricles and had three distinct and unique phases. Initially there was minimal neutrophil exudation and a two-day delay before any increase in macrophage-microglial cell number. Next, there was a rapid increase in macrophage-microglial cell numbers during the third day, mainly due to recruitment of blood monocytes. During this phase, leukocyte recruitment was restricted to monocytes which rapidly adopted the arborized microglial phenotype. Monocytes migrated through an intact blood-brain barrier independent of changes in solute permeability. Finally, there was a florid myelomonocytic reaction predominantly in the white matter, one week after intracerebral injection of 2-mu-g lipopolysaccharide. At this time, the leukocyte reaction disrupted the blood-brain barrier, mononuclear phagocytes expressed macrophage morphology and abundant major histocompatability complex Class II antigen, and T lymphocytes were present. Myelomonocytic entry into the CNS was partially inhibited by prior blockade of the type 3 complement receptor, known to mediate leukocyte adhesion to endothelium elsewhere.The processes which lead to rapid myelomonocytic recruitment in other tissues are absent in CNS parenchyma. Understanding the molecular mechanisms responsible could have considerable significance both for CNS pathophysiology as well as possible anti-inflammatory therapeutic application elsewhere in the body.