Complement activation in the central nervous system following blood-brain barrier damage in man
Complement activation in the central nervous system following blood-brain barrier damage in man
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DOI：
10.1002/ana.410400408
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发表时间：
1996-10-01
影响因子：
11.2
通讯作者：
Meri, S
中科院分区：
文献类型：
--
作者：
Lindsberg, PJ;Ohman, J;Meri, S
中枢神经系统（CNS）实际上与循环免疫因子如补体（C）分离，补体是体液免疫和炎症的重要介质。在循环中，C不断受到抑制，以防止对宿主细胞的攻击。由于许多疾病产生异常的血脑/脑脊液（血脑/CSF）渗透性，允许C蛋白外渗，我们研究了在蛛网膜下腔出血（SAH）或脑梗死期间，C激活是否发生在体外CSF和体内CNS中。SAH后（n = 15），CSF中第0 - 2天的终末补体复合物（TCC）浓度（210 +/- 61 ng/ml）高于血浆（63 +/- 17 ng/ml），但对照组（n = 8）或缺血性卒中患者（n = 7）的CSF中为零。SAH后TCC从CSF中消除（第7 - 10天为24 +/- 10 ng/ml）。正常人CSF与血清在体外孵育也激活了末端C途径。在10个致命的缺血性脑梗死，免疫组化技术表明，伴随着中性粒细胞浸润的C9神经元片段相关的沉积。我们的结论是，C系统成为激活鞘内SAH和局灶性脑实质缺血性中风。通过促进趋化性和血管扰动，C激活可能引发非免疫性炎症，并加重血浆外渗相关疾病的CNS损伤。
The central nervous system (CNS) is virtually isolated from circulating immunological factors such as complement (C), an important mediator of humoral immunity and inflammation. In circulation, C is constantly inhibited to prevent attack on host cells. Since a host of diseases produce an abnormal blood-brain/cerebrospinal fluid (blood-brain/CSF) permeability allowing C protein extravasation, we investigated if C activation occurs in CSF in vitro and in CNS in vivo during subarachnoid hemorrhage (SAH) or brain infarction. After SAH (n = 15), the terminal complement complex (TCC) concentration on days 0 to 2 was higher in the CSF, 210 +/- 61 ng/ml, than in the plasma, 63 +/- 17 ng/ml, but null in the CSF of controls (n = 8) or patients with an ischemic stroke (n = 7). TCC was eliminated from the CSF after SAH (24 +/- 10 ng/ml on days 7 to 10). Incubation of normal human CSF with serum in vitro also activated the terminal C pathway. In 10 fatal ischemic brain infarctions, immunohistochemical techniques demonstrated neuronal fragment-associated deposition of C9 accompanied by neutrophil infiltration. We conclude that the C system becomes activated intrathecally in SAH and focally in the brain parenchyma in ischemic stroke. By promoting chemotaxis and vascular perturbation, C activation may instigate nonimmune inflammation and aggravate CNS damage in diseases associated with plasma extravasation.