CCL2 transgene expression in the central nervous system directs diffuse infiltration of CD45high CD11b+ monocytes and enhanced Theiler's murine encephalomyelitis virus-induced demyelinating disease

Jami L. Bennett, Adam Elhofy, Mauro C. Dal Canto, Mari Tani, Richard M. Ransohoff, William J. Karpus*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

CCL2 is a member of the CC chemokine family that mediates the migration and recruitment of monocytes and T cells and has been identified in the central nervous system (CNS) during several neuroinflammatory diseases. In order to examine the biological effect of constitutive CCL2 expression in the CNS, the authors engineered a mouse that expressed CCL2 in the CNS under control of the human glial fibrillary acidic protein (hGFAP) promoter. The results demonstrated that transgenic expression of CCL2 in the CNS resulted in diffuse CNS monocyte infiltration and accumulation. Transgenic CCL2 expression did not alter normal development, differentiation, or function of T cells. There was no evidence of overt CNS disease or other pathologic phenotype when mice were left unchallenged with antigen or uninfected. However, when CCL2 transgenic mice were given a peripheral challenge of lipopolysaccharide (LPS), an inflammatory infiltrate with organized perivascular lesions developed. Infection of the transgenic mice with Theiler's murine encephalomyelitis virus (TMEV) resulted in accelerated onset and increased severity of clinical and histological disease. These results suggest that CCL2 expression in the CNS is a major pathogenic factor that drives macrophage accumulation in the development of CNS inflammatory disease.

Original languageEnglish (US)
Pages (from-to)623-636
Number of pages14
JournalJournal of neurovirology
Volume9
Issue number6
DOIs
StatePublished - Dec 2003

Keywords

  • CNS inflammation
  • Chemokines
  • Chemotaxis
  • Monocyte recruitment
  • Multiple sclerosis
  • Neuroinflammation

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

Fingerprint Dive into the research topics of 'CCL2 transgene expression in the central nervous system directs diffuse infiltration of CD45<sup>high</sup> CD11b<sup>+</sup> monocytes and enhanced Theiler's murine encephalomyelitis virus-induced demyelinating disease'. Together they form a unique fingerprint.

Cite this