Expression of endothelial adhesion molecules and recruitment of neutrophils after traumatic brain injury in rats
Expression of endothelial adhesion molecules and recruitment of neutrophils after traumatic brain injury in rats
复制标题
DOI：
10.1002/jlb.61.3.279
复制
发表时间：
1997-03-01
影响因子：
5.5
通讯作者：
Kochanekt, PM
中科院分区：
文献类型：
--
作者：
Carlos, TM;Clark, RSB;Kochanekt, PM
创伤性脑损伤 (TBI) 通常伴有最初由中性粒细胞介导的急性炎症反应，血管内皮上表达的粘附分子是炎症部位白细胞募集过程中的必要元素。在 TBI 大鼠模型中，脑血管内皮上 E-选择素 (CD62E) 的诱导和持续表达 证实了挫伤部位的同侧而非对侧（P < 0.05，在创伤后 4 小时和 48 小时），此外，这些研究证实了受创伤半球内皮细胞上 ICAM-1 (CD54) 的表达上调和延长（P < 0.05，在创伤后 4、24、48 和 72 小时）。有趣的是，CD54 表达增加是 创伤后 48 小时，在对侧、未受创伤的半球血管上观察到，第三种内皮粘附分子 PECAM-1 (CD31) 的表达在创伤后没有变化，给予抑制 CD54 粘附功能的鼠单克隆抗体 (TM-8) 阻断了很大一部分 (37.9%) 的中性粒细胞 创伤后 24 小时招募（P = 0.04），采用免疫细胞化学和大鼠中性粒细胞特异性单克隆抗体（RP-3），显示中性粒细胞浸润高峰发生在创伤后 48 小时，然而，与中性粒细胞从挫伤内血管迁移相反，中性粒细胞从周围的软脑膜进入 这些研究证明了 CD54 (ICAM-1) 在 TBI 后募集中性粒细胞中的相关性，然而，大多数中性粒细胞流入依赖于 CD54 以外的内皮粘附分子。由于中性粒细胞的迁移主要发生在软脑膜和脉络丛内的血管，鞘内递送抑制中性粒细胞、内皮CD54和待定义的其他内皮粘附分子之间粘附相互作用的药物可能提供一种新的治疗形式，以预防TBI后的急性炎症反应。
Traumatic brain injury (TBI) is often accompanied by an acute inflammatory reaction mediated initially by neutrophils, Adhesion molecules expressed on vascular endothelium are requisite elements during recruitment of leukocytes at sites of inflammation., In a rat model of TBI the induction and persistent expression of E-selectin (CD62E) on cerebrovascular endothelium ipsilateral, but not contralateral, to the site of contusion was demonstrated (P < 0.05 at 4 and 48 h posttrauma), In addition, these studies confirmed up-regulation and prolonged expression of ICAM-1 (CD54) on endothelium in the traumatized hemisphere (P < 0.05 at 4, 24, 48, and 72 h posttrauma), It is of interest that increased expression of CD54 was noted on blood vessels in the contralateral, non-traumatized hemisphere 48 h posttrauma, Expression of a third endothelial adhesion molecule, PECAM-1 (CD31), was unchanged following trauma, Administration of a murine monoclonal antibody (TM-8) that inhibits the adhesive function of CD54 blocked a significant portion (37.9%) of neutrophil recruitment 24 h posttrauma (P = 0.04), Employing immunocytochemistry and a monoclonal antibody specific for rat neutrophils (RP-3), peak infiltration of neutrophils was shown to occur 48 h after trauma, In contrast to emigration of neutrophils from blood vessels within the contusion, however, entry of neutrophils occurred from the surrounding leptomeninges and choroidal vessels, These studies demonstrate the relevance of CD54 (ICAM-1) in recruitment of neutrophils following TBI, However, the majority of neutrophil influx relies on endothelial adhesion molecules other than CD54. Because emigration of neutrophils was shown to occur predominantly from vessels within the leptomeninges and choroid plexus, intrathecal delivery of agents that inhibit the adhesive interactions between neutrophils, endothelial CD54, and other endothelial adhesion molecules to be defined may offer a novel form of therapy to prevent the acute inflammatory response that follows TBI.