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

Kohei Sonoda, Takeru Yoshimura, Kensuke Egashira, Israel F. Charo, Tatsuro Ishibashi

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Purpose: 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.

Original languageEnglish
JournalActa Ophthalmologica
Volume89
Issue number2
DOIs
Publication statusPublished - Mar 1 2011

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CCR2 Receptors
Uveitis
Knockout Mice
Neutrophils
Macrophages
Flow Cytometry
Chemokine CXCL10
Monokines
CXC Chemokines
Peptides
Freund's Adjuvant
Chemokine CCL2
Chemokines
Interferons
Immunization
Histology
Animal Models
Observation

All Science Journal Classification (ASJC) codes

  • Ophthalmology

Cite this

Neutrophil-dominant experimental autoimmune uveitis in CC-chemokine receptor 2 knockout mice. / Sonoda, Kohei; Yoshimura, Takeru; Egashira, Kensuke; Charo, Israel F.; Ishibashi, Tatsuro.

In: Acta Ophthalmologica, Vol. 89, No. 2, 01.03.2011.

Research output: Contribution to journalArticle

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