Altered vascular permeability and early onset of experimental autoimmune encephalomyelitis in PECAM-1-deficient mice
Altered vascular permeability and early onset of experimental autoimmune encephalomyelitis in PECAM-1-deficient mice
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DOI：
10.1172/jci13595
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发表时间：
2002-02-01
影响因子：
15.9
通讯作者：
Madri, JA
中科院分区：
文献类型：
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作者：
Graesser, D;Solowiej, A;Madri, JA
血小板/内皮细胞粘附分子-1 （PECAM-1,CD31）是跨膜蛋白Ig超家族的一个130 kda的糖蛋白成员，在内皮细胞、血小板和白细胞亚群上表达。它作为细胞粘附分子以及能够调节细胞信号通路的支架分子发挥作用。在这项研究中，我们使用PECAM-1缺陷（KO）小鼠以及来源于这些小鼠的细胞，证明了PECAM-1表达缺失与实验性自身免疫性脑脊髓炎（EAE）（人类自身免疫性疾病多发性硬化症的小鼠模型）期间临床症状的早期发作有关。在EAE期间，PECAM-KO小鼠比野生型小鼠在更早的时间点发生单核细胞外渗和中枢神经系统浸润。在体外，无论PECAM-1在迁移的T细胞上的表达如何，T淋巴细胞在PECAM-KO内皮细胞上的跨内皮迁移都被增强。此外，与pecam -1重组内皮细胞相比，培养的PECAM-KO内皮细胞在组胺处理下表现出较长时间的通透性变化。最后，我们在PECAM-KO小鼠中证明了EAE发展过程中CNS血管通透性的夸大和延长，以及组胺刺激后真皮血管完整性恢复的延迟。
Platelet/endothelial cell adhesion molecule-1 (PECAM-1,CD31), a 130-kDa glycoprotein member of the Ig superfamily of transmembrane proteins, is expressed on endothelial cells, platelets, and subsets of leukocytes. It functions as a cell adhesion molecule as well as a scaffolding molecule capable of modulating cellular signaling pathways. In this study, using PECAM-1-deficient (KO) mice as well as cells derived from these mice, we demonstrate that the absence of PECAM-1 expression is associated with an early onset of clinical symptoms during experimental autoimmune encephalomyelitis (EAE), a mouse model for the human autoimmune disease multiple sclerosis. During EAE, mononuclear cell extravasation and infiltration of the CNS occur at earlier time points in PECAM-KO mice than in wild-type mice. In vitro, T lymphocyte transendothelial migration across PECAM-KO endothelial cells is enhanced, regardless of expression of PECAM-1 on transmigrating T cells. Additionally, cultured PECAM-KO endothelial cells exhibit prolonged permeability changes in response to histamine treatment compared with PECAM-1-reconstituted endothelial cells. Lastly, we demonstrate an exaggerated and prolonged CNS vascular permeability during the development of EAE and a delay in restoration of dermal vascular integrity following histamine challenge in PECAM-KO mice.