CXCR2-positive Neutrophils Are Essential for Cuprizone-induced Demyelination: Relevance to Multiple Sclerosis

Overview

Journal Nat Neurosci

Date 2010 Feb 16

PMID 20154684

Citations 117

Authors

Liping Liu

Abdelmadjid Belkadi

Lindsey Darnall

Taofang Hu

Caitlin Drescher

Anne C Cotleur

Dolly Padovani-Claudio

Tao He

Karen Choi

Thomas E Lane

Robert H Miller

Richard M Ransohoff

Affiliations

Soon will be listed here.

Abstract

Multiple sclerosis is an inflammatory demyelinating disorder of the CNS. Recent studies have suggested diverse mechanisms as underlying demyelination, including a subset of lesions induced by an interaction between metabolic insult to oligodendrocytes and inflammatory mediators. For mice of susceptible strains, cuprizone feeding results in oligodendrocyte cell loss and demyelination of the corpus callosum. Remyelination ensues and has been extensively studied. Cuprizone-induced demyelination remains incompletely characterized. We found that mice lacking the type 2 CXC chemokine receptor (CXCR2) were relatively resistant to cuprizone-induced demyelination and that circulating CXCR2-positive neutrophils were important for cuprizone-induced demyelination. Our findings support a two-hit process of cuprizone-induced demyelination, supporting the idea that multiple sclerosis pathogenesis features extensive oligodendrocyte cell loss. These data suggest that cuprizone-induced demyelination is useful for modeling certain aspects of multiple sclerosis pathogenesis.

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