dos Santos Adriana Carvalho, Barsante Michele Mendes, Arantes Rosa Maria Esteves, Bernard Claude C A, Teixeira Mauro Martins, Carvalho-Tavares Juliana
Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
J Neuroimmunol. 2005 May;162(1-2):122-9. doi: 10.1016/j.jneuroim.2005.01.020.
Experimental autoimmune encephalomyelitis (EAE) models multiple sclerosis (MS) and is characterized by marked mononuclear cell influx in the brain. Several studies have demonstrated a role for chemokines during EAE. It remains to be determined whether these mediators modulate EAE primarily by mediating leukocyte influx into the CNS or by modifying lymphocyte activation and/or trafficking into lymphoid organs. After induction of EAE with MOG(35-55), leukocyte recruitment peaked on day 14 and correlated with symptom onset, TNF-alpha production and production of CCL2 and CCL5. Levels of CXCL-10 and CCL3 were not different from control animals. Using intravital microscopy, we demonstrated that leukocyte rolling and adhesion also peaked at day 14. Treatment with anti-CCL2 or anti-CCL5 antibodies just prior to the intravital microscopy prevented leukocyte adhesion, but not rolling. Our data suggest that induction of leukocyte adhesion to the brain microvasculature is an important mechanism by which CCL2 and CCL5 participate in the pathophysiology of EAE.
实验性自身免疫性脑脊髓炎（EAE）是多发性硬化症（MS）的模型，其特征是大脑中有明显的单核细胞浸润。多项研究已证明趋化因子在EAE过程中发挥作用。这些介质是否主要通过介导白细胞流入中枢神经系统（CNS），或通过改变淋巴细胞激活和/或进入淋巴器官的运输来调节EAE，仍有待确定。在用髓鞘少突胶质细胞糖蛋白（MOG(35-55)）诱导EAE后，白细胞募集在第14天达到峰值，并与症状发作、肿瘤坏死因子-α（TNF-α）产生以及趋化因子CCL2和CCL5的产生相关。CXCL-10和CCL3的水平与对照动物没有差异。使用活体显微镜检查，我们证明白细胞滚动和黏附也在第14天达到峰值。在进行活体显微镜检查之前用抗CCL2或抗CCL5抗体治疗可防止白细胞黏附，但不能防止滚动。我们的数据表明，诱导白细胞黏附于脑微血管是CCL2和CCL5参与EAE病理生理过程的重要机制。
