Effector stage CC chemokine receptor-1 selective antagonism reduces multiple sclerosis-like rat disease

被引：31

作者：

Eltayeb, S

Sunnemark, D

Berg, AL

Nordvall, G

Malmberg, Å

Lassmann, H

Wallström, E

Olsson, T

Ericsson-Dahlstrand, A

机构：

[1] Karolinska Inst, Dept Med, Neuroimmunol Unit, SE-17176 Stockholm, Sweden

[2] RA CNS & Pain Control, AstraZeneca R&D Sodertalje, Dept Mol Sci, SE-15185 Sodertalje, Sweden

[3] AstraZeneca R&D Sodertalje, Safety Assessment, Dept Pathol, SE-15185 Sodertalje, Sweden

[4] AstraZeneca R&D Sodertalje, Dept Chem, SE-15185 Sodertalje, Sweden

[5] RA CNS & Pain Control, AstraZeneca R&D Sodertalje, Dept Lead Discovery, SE-15185 Sodertalje, Sweden

[6] Univ Vienna, Inst Brain Res, A-1090 Vienna, Austria

[7] Karolinska Inst, Dept Med, Rheumatol Unit, SE-17176 Stockholm, Sweden

来源：

JOURNAL OF NEUROIMMUNOLOGY | 2003年 / 142卷 / 1-2期

关键词：

multiple sclerosis; chemokines; macrophages; demyelination; inflammation; receptor;

D O I：

10.1016/S0165-5728(03)00264-9

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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-1alpha) 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. (C) 2003 Elsevier B.V. All rights reserved.

引用

页码：75 / 85

页数：11

共 46 条

[31] Discovery of novel non-peptide CCR1 receptor antagonists [J].