RGD Reference Report - Development of experimental autoimmune uveitis: efficient recruitment of monocytes is independent of CCR2. - Rat Genome Database

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Development of experimental autoimmune uveitis: efficient recruitment of monocytes is independent of CCR2.

Authors: Dagkalis, A  Wallace, C  Xu, H  Liebau, S  Manivannan, A  Stone, MA  Mack, M  Liversidge, J  Crane, IJ 
Citation: Dagkalis A, etal., Invest Ophthalmol Vis Sci. 2009 Sep;50(9):4288-94. doi: 10.1167/iovs.09-3434. Epub 2009 Apr 8.
RGD ID: 8657383
Pubmed: PMID:19357362   (View Abstract at PubMed)
DOI: DOI:10.1167/iovs.09-3434   (Journal Full-text)

PURPOSE: Macrophages are major contributors to the damage occurring in the retina in experimental autoimmune uveitis (EAU). CCR2 may be needed for efficient recruitment of monocytes to an inflammatory site, and the aim of this study was to determine whether this was the case in EAU. METHODS: EAU was induced and graded in C57BL/6J and CCR2(-/-) mice. Macrophage infiltration and CCR2 expression were assessed using immunohistochemistry. Retinas were examined for MCP-1 expression using RT-PCR. Rolling and infiltration of labeled bone marrow monocytes at the inflamed retinal vasculature were examined by scanning laser ophthalmoscopy and confocal microscopy, respectively. Effect of CCR2 deletion or blockade by antibody and antagonist was determined. RESULTS: Expression of mRNA for MCP-1 increased as EAU developed and was localized to the retina. CCR2 was associated with infiltrating macrophages. However, EAU induced in CCR2(-/-) mice was not reduced in severity, and neither was the percentage of macrophages in the retina. CCR2(-/-) monocytes, 48 hours after adoptive transfer to mice with EAU, showed no significant difference in percentage rolling or infiltration into the retina compared to WT. CCR2-independent rolling of monocytes was confirmed by CCR2 neutralizing antibody and antagonist treatment. CONCLUSIONS: CCR2 does not have a primary role in the recruitment of monocytes to the inflammatory site across the blood-retina barrier in well-developed EAU. Therapeutics targeting CCR2 are unlikely to be of value in treating human posterior uveitis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Autoimmune Uveitis no_associationISOCcr2 (Mus musculus)8657383; 8657383 RGD 
Experimental Autoimmune Uveitis no_associationIMP 8657383 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccr2  (C-C motif chemokine receptor 2)

Genes (Mus musculus)
Ccr2  (C-C motif chemokine receptor 2)

Genes (Homo sapiens)
CCR2  (C-C motif chemokine receptor 2)


Additional Information