Administration of a monomeric CCL2 variant to EAE mice inhibits inflammatory cell recruitment and protects from demyelination and axonal loss

被引：21

作者：

Brini, E.

Ruffini, F.

Bergami, A.

Brambilla, E.

Dati, G. ^{[3
]}

Greco, B. ^{[3
]}

Cirillo, R. ^{[3
]}

Proudfoot, A. E. I. ^{[4
]}

Comi, G. ^{[2
]}

Furlan, R. ^{[1
,2
]}

Zaratin, P. ^{[3
]}

Martino, G. ^{[2
]}

机构：

[1] Ist Sci San Raffaele, Neuroimmunol Unit, INSpe, I-20132 Milan, Italy

[2] Ist Sci San Raffaele, Dept Neurol, I-20132 Milan, Italy

[3] RMB Merck Serono Int SA, Turin, Italy

[4] Merck Serono Int SA, Geneva, Switzerland

来源：

JOURNAL OF NEUROIMMUNOLOGY | 2009年 / 209卷 / 1-2期

关键词：

EAE/MS; Chemokines; CCL2; CCR2; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MONOCYTE CHEMOATTRACTANT PROTEIN-1; CENTRAL-NERVOUS-SYSTEM; CHEMOKINE RECEPTOR EXPRESSION; MULTIPLE-SCLEROSIS PATIENTS; BLOOD-BRAIN-BARRIER; CHEMOTACTIC PROTEIN-1; T-CELLS; CEREBROSPINAL-FLUID; MCP-1; RECEPTOR;

D O I：

10.1016/j.jneuroim.2009.01.022

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Based on gene expression data, we tested the P8A-CCL2 variant of the chemokine CCL2, able to interfere with the chemotactic properties of the parental molecule, in relapsing-remitting (RR)-EAE SJL Only preventive treatment significantly delayed disease onset in a dose dependent manner. P8A-CCL2 administration, however, decreased demyelination, axonal loss and number of CNS infiltrating T cells and macrophages. Immunological analysis revealed that P8A-CCL2 does not act on Ag-specific T cell proliferation and does not interfere with the differentiation of IFN gamma-releasing effectors T cells. These results suggest that the therapeutic mechanism of P8A-CCL2 may rely on interference with immune cell recruitment. (C) 2009 Elsevier B.V. All rights reserved.

引用

页码：33 / 39

页数：7

共 44 条

[1] CCR5+ and CXCR3+ T cells are increased in multiple sclerosis and their ligands MIP-1α and IP-10 are expressed in demyelinating brain lesions [J].