Experimental autoimmune encephalomyelitis (EAE) in CCR2(-/-) mice: susceptibility in multiple strains.

  • Gaupp S
  • Pitt D
  • Kuziel W
 et al. 
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Abstract

Chemokines are low molecular weight cytokines which act as chemoattractants for infiltrating cells bearing appropriate receptors (CCR) to sites of inflammation. It has been proposed that CCR2 on monocytes is responsible for their recruitment into the central nervous system (CNS) in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis, and two previous reports have described resistance of CCR2(-/-) mice to EAE. The present study examined three different mouse strains with CCR2 deletions for susceptibility to EAE. Animals were studied up to 4 months post-sensitization and were examined by neuropathology, RNase protection assay, in situ hybridization, and in vitro assays. All three strains were found to be susceptible to EAE: C57BL/6 x J129 and Balb c strains, 100%; and C57BL/6, 67%. Unusual in CNS lesions of CCR2(-/-) mice was an overabundance of neutrophils versus monocytes in wild-type animals. An attempt of the immune system to develop compensatory mechanisms for the lack of CCR2 was evidenced by a corresponding increase in mRNA for other chemokines and CCR. Inasmuch as neutrophils replaced monocytes and led to demyelination, our findings support the concept that promiscuity of chemokines and CCR was able to surmount the deletion of CCR2, still resulting in full expression of this autoimmune disease.

Author-supplied keywords

  • Animals
  • Cell Division
  • Cell Division: immunology
  • Crosses, Genetic
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental
  • Encephalomyelitis, Autoimmune, Experimental: genet
  • Encephalomyelitis, Autoimmune, Experimental: immun
  • Encephalomyelitis, Autoimmune, Experimental: patho
  • Genetic Predisposition to Disease
  • Glycoproteins
  • Glycoproteins: immunology
  • Immunity, Innate
  • Immunity, Innate: genetics
  • Immunohistochemistry
  • In Situ Hybridization
  • Lymphocytes
  • Lymphocytes: immunology
  • Lymphocytes: pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Knockout
  • Myelin Sheath
  • Myelin Sheath: immunology
  • Myelin Sheath: metabolism
  • Myelin-Oligodendrocyte Glycoprotein
  • Nuclease Protection Assays
  • Peptide Fragments
  • Peptide Fragments: immunology
  • RNA, Messenger
  • RNA, Messenger: metabolism
  • Receptors, CCR2
  • Receptors, Chemokine
  • Receptors, Chemokine: biosynthesis
  • Receptors, Chemokine: deficiency
  • Receptors, Chemokine: genetics
  • Species Specificity

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Authors

  • Stefanie Gaupp

  • David Pitt

  • William A Kuziel

  • Barbara Cannella

  • Cedric S Raine

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