Overriding the brain's intrinsic resistance to leukocyte recruitment with intraparenchymal injections of recombinant chemokines
Overriding the brain's intrinsic resistance to leukocyte recruitment with intraparenchymal injections of recombinant chemokines
复制标题
DOI：
10.1016/0306-4522(96)00083-8
复制
发表时间：
1996-09-01
期刊：
影响因子：
3.3
通讯作者：
Perry, VH
中科院分区：
文献类型：
--
作者：
Bell, MD;Taub, DD;Perry, VH
在脑内注射脂多糖后或在急性神经元变性期间，多形核白细胞在脑实质中的募集稀少，单核细胞募集延迟。本研究旨在探讨向小鼠中枢神经系统注射特定的白细胞趋化剂是否可以克服这种固有的抵抗力。将重组α-趋化因子(IL-8/NAP-1、MIP-2、IP-10)和β-趋化因子(MCP-I、RANTES)注入小鼠海马区，组织学检测白细胞募集情况。后侧真皮内注射作为对照。在1ug剂量下，MCP-I被发现是脑实质和皮肤中最有效的单核细胞趋化剂，IP-IO和RANTES对这两个部位的单核细胞募集最少。相比之下，IL-8和MIP-2在中枢神经系统和皮肤中都能显著刺激多形核白细胞的募集。多形核白细胞募集与血脑屏障的破坏有关，在MIP-2后尤为严重。L-8和MIP-2诱导的血脑屏障破坏均可通过预先去除循环中的白细胞而减轻，脑实质中多形核白细胞趋化因子在损伤和感染过程中的调控是未来研究的重要领域。版权所有(C)1996，爱思唯尔科学有限公司出版。
Following the intracranial injection of lipopolysaccharide or during acute neuronal degeneration, there is a paucity of polymorphonuclear leukocyte recruitment to the brain parenchyma and a delay in monocyte recruitment. The present study investigates whether the injection of specific leukocyte chemoattractants into the murine central nervous system can override this intrinsic resistance. Recombinant alpha-(IL-8/NAP-1, MIP-2, IP-10) and beta-chemokines (MCP-I, RANTES) were injected into the murine hippocampus and leukocyte recruitment was assessed histologically. Injections were also made into the dermis of the hind flank for comparison. At doses of I mu g, MCP-I was found to be the most potent monocyte chemoattractant in the brain parenchyma and skin with IP-IO and RANTES producing minimal monocyte recruitment to both sites. In contrast IL-8, and MIP-2 provoked dramatic polymorphonuclear leukocyte recruitment in both the central nervous system and skin. The polymorphonuclear leukocyte recruitment was associated with a breaching of the blood-brain barrier that was particularly severe after MIP-2. Both L-8 and MIP-2 induced blood-brain barrier breakdown could be attenuated by prior depletion of the circulating leukocytes.The regulation of polymorphonuclear leukocyte chemoattractants in the brain parenchyma during injury and infection is an important area for future studies. Copyright (C) 1996 Published by Elsevier Science Ltd.