Deletion of both ICAM-1 and C3 enhances severity of experimental autoimmune encephalomyelitis compared to C3-deficient mice.
Deletion of both ICAM-1 and C3 enhances severity of experimental autoimmune encephalomyelitis compared to C3-deficient mice.
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DOI：
10.1016/j.neulet.2008.07.005
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发表时间：
2008-09-12
影响因子：
2.5
通讯作者：
Barnum SR
中科院分区：
文献类型：
--
作者：
Smith SS;Ludwig M;Wohler JE;Bullard DC;Szalai AJ;Barnum SR
多发性硬化（MS）是一种自身免疫性疾病，其特征在于中枢神经系统（CNS）炎症和白细胞浸润、神经元脱髓鞘和血脑屏障破坏。实验性自身免疫性脑脊髓炎（EAE），MS的动物模型的发展依赖于免疫系统的许多组分，包括补体和粘附分子。我们实验室以前的研究已经检查了C3（中心补体成分）和细胞间粘附分子-1（ICAM-1）（一种参与白细胞运输到炎症部位（包括CNS）的关键细胞粘附分子）的作用。在这些研究中，我们证明了髓鞘少突胶质细胞糖蛋白（MOG）诱导的EAE在ICAM-1−/−和C3−/−小鼠中均显著减弱。鉴于这些蛋白质在EAE中发挥的关键作用，我们假设ICAM-1−/−和C3−/−双突变小鼠中的EAE可能不会发生。出乎意料的是，ICAM-1−/− × C3−/−小鼠中的EAE与野生型小鼠相比仅适度减弱，并且比C3−/−小鼠明显更差。白细胞浸润与三组小鼠之间的疾病严重程度相当。来自ICAM-1−/− × C3−/−小鼠的脊髓T细胞产生最高水平的IFN-γ和TNF-α，尽管与野生型小鼠相比疾病严重程度降低。ICAM-1−/− × C3−/−小鼠EAE严重程度升高的机制可能与白细胞归巢改变或双突变背景下自身抗原的处理有关。
Multiple sclerosis (MS) is an autoimmune disease characterized by central nervous system (CNS) inflammation and leukocyte infiltration, demyelination of neurons, and blood-brain barrier breakdown. The development of experimental autoimmune encephalomyelitis (EAE), the animal model for MS is dependent on a number of components of the immune system including complement and adhesion molecules. Previous studies in our lab have examined the role of C3, the central complement component, and intercellular adhesion molecule-1 (ICAM-1) a key cell adhesion molecule involved in leukocyte trafficking to sites of inflammation including the CNS. In these studies we demonstrated that myelin oligodendrocyte glycoprotein (MOG)-induced EAE is markedly attenuated in both ICAM-1−/− and C3−/− mice. Given the pivotal role that these proteins play in EAE, we hypothesized that EAE in ICAM-1−/− and C3−/− double mutant mice would likely fail to develop. Unexpectedly, EAE in ICAM-1−/− × C3−/− mice was only modestly attenuated compared to wild type mice and significantly worse than C3−/− mice. Leukocyte infiltration was commensurate with disease severity between the three groups of mice. Spinal cord T cells from ICAM-1−/− × C3−/− mice produced the highest levels of IFN-γ and TNF-α, despite reduced disease severity compared to wild type mice. The mechanisms behind the elevated EAE severity in ICAM-1−/− × C3−/− mice may relate to altered homing of leukocytes or processing of self-antigens in the double mutant background.
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影响因子：
4.4
作者：
Bullard, DC;Hu, XZ;Barnum, SR
通讯作者：
Barnum, SR
影响因子：
6
作者：
Bullard, Daniel C.;Hu, Xianzhen;Barnum, Scott R.
通讯作者：
Barnum, Scott R.
病毒和自我抗原的新颖包装是在凋亡过程中产生的。
影响因子：
15.3
作者：
Rosen, Antony;Casciola-Rosen, Livia;Ahearn, Joseph
通讯作者：
Ahearn, Joseph
DOI：
10.1016/s0162-3109(99)00021-1
发表时间：
1999-05-01
期刊：
IMMUNOPHARMACOLOGY
影响因子：
--
作者：
Circolo, A;Garnier, G;Colten, HR
通讯作者：
Colten, HR
实验性自身免疫性脑脊髓炎中γδ和αβ T 细胞之间β2-整合素的差异表达和细胞因子的产生
影响因子：
5.5
作者：
Smith, Sherry S.;Barnum, Scott R.
通讯作者：
Barnum, Scott R.