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Neutrophil-dominant experimental autoimmune uveitis in CC-chemokine receptor 2 knockout mice.

AbstractPURPOSE:
Murine experimental autoimmune uveitis (EAU) is an animal model of human uveitis. It has been demonstrated that ocular-infiltrating macrophages are crucial for EAU induction, and monocyte chemoattractant protein-1 (MCP-1) was actually upregulated in the eye. CC chemokine receptor-2 (CCR2) is the receptor of MCP-1, and macrophages fail to recruit particular lesions in CCR2 knockout (KO) mice. To confirm the role of macrophages in EAU, we examined EAU in CCR2 KO mice.
METHODS:
CCR2 KO mice and wild-type (WT) mice that had the same genetic background were immunized with human interphotoreceptor retinoid-binding protein peptide 1-20 emulsified in complete Freund's adjuvant. At multiple time-points, EAU severity was evaluated based on microscopic fundus observation and histological examination. To examine the phenotype of retinal-infiltrating cells, single cells were prepared from the eye and analysed by flow cytometry.
RESULTS:
In WT mice, EAU was induced at the peak of day 16 and marked macrophage infiltration was observed. Although macrophages failed to be recruited into the eye in CCR2 KO mice, severe uveitis was induced unexpectedly. Flow cytometry and histology revealed that most of the infiltrating cells were neutrophils. We also compared the intraocular chemokine concentrations between WT mice and KO mice. Two CXC chemokine (monokine induced by interferon-γ and interferon-γ-inducible protein-10) were upregulated in KO mice.
CONCLUSION:
Interphotoreceptor retinoid-binding protein peptide immunization caused neutrophil-dominant uveitis in CCR2 KO mice. In the absence of macrophages, neutrophils can be alternatively recruited and can cause tissue damage.
AuthorsKoh-Hei Sonoda, Takeru Yoshimura, Kensuke Egashira, Israel F Charo, Tatsuro Ishibashi
JournalActa ophthalmologica (Acta Ophthalmol) Vol. 89 Issue 2 Pg. e180-8 (Mar 2011) ISSN: 1755-3768 [Electronic] England
PMID20584001 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2010 The Authors. Journal compilation © 2010 Acta Ophthalmol.
Chemical References
  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Cytokines
  • Eye Proteins
  • Receptors, CCR2
  • Retinol-Binding Proteins
  • interstitial retinol-binding protein
Topics
  • Animals
  • Autoimmune Diseases (immunology)
  • Chemokine CCL2 (immunology)
  • Cytokines (immunology)
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Eye Proteins
  • Female
  • Flow Cytometry
  • Immunophenotyping
  • Macrophages (immunology)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophils (immunology)
  • Receptors, CCR2 (physiology)
  • Retinitis (immunology)
  • Retinol-Binding Proteins
  • Th1 Cells (immunology)
  • Uveitis, Posterior (immunology)

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