Department of Pathology and Diagnostics, Section of General Pathology, University of Verona, Strada le Grazie 8, 37134 Verona, Italy.
J Leukoc Biol. 2011 Apr;89(4):539-56. doi: 10.1189/jlb.0710432. Epub 2010 Dec 17.
Leukocyte trafficking from the blood into the tissues represents a key process during inflammation and requires multiple steps mediated by adhesion molecules and chemoattractants. Inflammation has a detrimental role in several diseases, and in such cases, the molecular mechanisms controlling leukocyte migration are potential therapeutic targets. Over the past 20 years, leukocyte migration in the CNS has been investigated almost exclusively in the context of stroke and MS. Experimental models of ischemic stroke have led to the characterization of adhesion molecules controlling leukocyte migration during acute inflammation, whereas EAE, the animal model of MS, has provided similar data for chronic inflammation. Such experiments have led to clinical trials of antileukocyte adhesion therapy, with consistently positive outcomes in human subjects with MS, showing that interference with leukocyte adhesion can ameliorate chronic inflammatory CNS diseases. This review summarizes our current understanding of the roles of adhesion molecules controlling leukocyte-endothelial interactions in stroke and MS, focusing on recently discovered, novel migration mechanisms. We also discuss the growing evidence suggesting a role for vascular inflammation and leukocyte trafficking in neurodegenerative diseases such as AD. Moreover, we highlight recent findings suggesting a role for leukocyte-endothelial interactions in the pathogenesis of seizures and epilepsy, thus linking endothelial activation and leukocyte trafficking to neuronal electrical hyperactivity. These emerging roles for leukocytes and leukocyte adhesion mechanisms in CNS diseases provide insight into the mechanisms of brain damage and may contribute to the development of novel therapeutic strategies.
白细胞从血液向组织中的迁移是炎症过程中的一个关键步骤，需要通过粘附分子和趋化因子介导的多个步骤。炎症在多种疾病中起有害作用，在这种情况下，控制白细胞迁移的分子机制是潜在的治疗靶点。在过去的 20 年中，CNS 中的白细胞迁移几乎仅在中风和 MS 的背景下进行了研究。缺血性中风的实验模型导致了控制急性炎症期间白细胞迁移的粘附分子的特征，而 EAE，MS 的动物模型，为慢性炎症提供了类似的数据。这些实验导致了抗白细胞粘附治疗的临床试验，在 MS 人类受试者中始终具有积极的结果，表明干扰白细胞粘附可以改善慢性炎症性 CNS 疾病。这篇综述总结了我们目前对控制白细胞-内皮相互作用的粘附分子在中风和 MS 中的作用的理解，重点介绍了最近发现的新型迁移机制。我们还讨论了越来越多的证据表明血管炎症和白细胞迁移在 AD 等神经退行性疾病中的作用。此外，我们强调了最近的发现表明白细胞-内皮相互作用在癫痫发作和癫痫的发病机制中的作用，从而将内皮激活和白细胞迁移与神经元电过度活动联系起来。白细胞和白细胞粘附机制在 CNS 疾病中的这些新作用提供了对脑损伤机制的深入了解，并可能有助于开发新的治疗策略。
