Eltayeb Sana, Sunnemark Dan, Berg Anna-Lena, Nordvall Gunnar, Malmberg Asa, Lassmann Hans, Wallström Erik, Olsson Tomas, Ericsson-Dahlstrand Anders
Neuroimmunology Unit, Department of Medicine, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
J Neuroimmunol. 2003 Sep;142(1-2):75-85. doi: 10.1016/s0165-5728(03)00264-9.
We have studied the role of the chemokine receptor CCR1 during the effector stage of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in DA rats. In situ hybridization histochemistry revealed local production of the CCR1 ligands CCL3 (MIP-1 alpha) and CCL5 (RANTES), as well as large numbers of CCR1 and CCR5 expressing cells within inflammatory brain lesions. A low-molecular weight CCR1 selective antagonist potently abrogated both clinical and histopathological disease signs during a 5-day treatment period, without signs of peripheral immune compromise. Thus, we demonstrate therapeutic targeting of CCR1-dependent leukocyte recruitment to the central nervous system in a multiple sclerosis (MS)-like rat model.
我们研究了趋化因子受体CCR1在髓鞘少突胶质细胞糖蛋白诱导的DA大鼠实验性自身免疫性脑脊髓炎效应阶段的作用。原位杂交组织化学显示CCR1配体CCL3（MIP-1α）和CCL5（RANTES）的局部产生，以及炎症性脑损伤内大量表达CCR1和CCR5的细胞。一种低分子量CCR1选择性拮抗剂在5天的治疗期内有效消除了临床和组织病理学疾病体征，且无外周免疫受损迹象。因此，我们在类多发性硬化症（MS）大鼠模型中证明了针对CCR1依赖性白细胞向中枢神经系统募集的治疗靶点。
