REDUCTION OF INFLAMMATION, TISSUE-DAMAGE, AND MORTALITY IN BACTERIAL-MENINGITIS IN RABBITS TREATED WITH MONOCLONAL-ANTIBODIES AGAINST ADHESION-PROMOTING RECEPTORS OF LEUKOCYTES
REDUCTION OF INFLAMMATION, TISSUE-DAMAGE, AND MORTALITY IN BACTERIAL-MENINGITIS IN RABBITS TREATED WITH MONOCLONAL-ANTIBODIES AGAINST ADHESION-PROMOTING RECEPTORS OF LEUKOCYTES
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DOI：
10.1084/jem.170.3.959
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发表时间：
1989-09-01
影响因子：
15.3
通讯作者：
WRIGHT, SD
中科院分区：
文献类型：
--
作者：
TUOMANEN, EI;SAUKKONEN, K;WRIGHT, SD
在兔实验性脑膜炎模型中，我们测试了特异性地抑制白细胞跨越血脑屏障从血管腔到脑脊液(CSF)间隙的招募是否减少了组织损伤并改善了感染的结局。白细胞上的CD11/CD18受体复合体促进这些细胞与内皮细胞的黏附，这是细胞进入血管外空间所需的过程。静脉注射抗CD18单抗IB4有效地阻止了活菌、细菌内毒素或细菌细胞壁攻击的动物脑脊液中白细胞增多的发展。这种作用与保护血脑屏障损伤有关，这是通过从mAb处理的动物的脑脊液中排除血清蛋白来衡量的。抗体对脑脊液细菌密度和氨苄西林杀菌作用无明显影响。在氨苄西林诱导的细菌杀灭过程中，接受抗体的动物经历了菌血症发展的延迟和炎症反应的显著减少。在致死剂量肺炎链球菌攻击的动物中，用单抗IB4治疗可防止脑水肿的发展和死亡。这些研究表明，白细胞跨血脑屏障迁移的主要机制涉及CD11/CD18受体，通过该机制募集的炎性白细胞是脑膜炎时血脑屏障损伤和脑水肿的主要原因。
We tested if specific inhibition of recruitment of leukocytes across the blood brain barrier from the vascular compartment to the cerebrospinal fluid (CSF) space reduced tissue damage and improved the outcome of infection in a rabbit model of experimental meningitis. The CD11/CD18 complex of receptors on leukocytes promotes adhesion of these cells to endothelia, a process required for egress of cells into the extravascular space. Intravenous injection of the anti-CD18 mAb IB4 effectively blocked the development of leukocytosis in the CSF of animals challenged intracisternally with living bacteria, bacterial endotoxin, or bacterial cell wall. This effect was associated with protection from blood brain barrier injury as measured by exclusion of serum proteins from CSF in mAb-treated animals. The densities of bacteria in CSF and the degrees of bacterial killing due to ampicillin were not affected by the antibody. Animals receiving the antibody experienced a delay in the development of bacteremia and a significantly reduced inflammatory response during ampicillin-induced bacterial killing. Therapy with mAb IB4 prevented development of brain edema and death in animals challenge with lethal doses of Streptococcus pneumoniae. These studies indicate that the major mechanism of leukocyte migration across the blood brain barrier involves the CD11/CD18 receptors and that inflammatory leukocytes recruited by this mechanism are a major cause of blood brain barrier injury and cerebral edema during meningitis.