PMID- 12091424
OWN - NLM
STAT- MEDLINE
DCOM- 20020715
LR  - 20220410
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 43
IP  - 7
DP  - 2002 Jul
TI  - Retinal microenvironment controls resident and infiltrating macrophage function 
      during uveoretinitis.
PG  - 2250-7
AB  - PURPOSE: Macrophages infiltrating an inflamed or injured tissue undergo 
      development of coordinated sets of properties that contribute to tissue damage, 
      repair, and remodeling. The purpose of this study was to determine whether 
      macrophages isolated from normal or inflamed retina are programmed to a distinct 
      set of properties and to examine whether the development of experimental 
      autoimmune uveoretinitis (EAU) affects macrophage function. METHODS: EAU was 
      induced in Lewis rats, and a retina-derived macrophage-enriched population was 
      generated by density centrifugation during the prepeak, peak, and resolution 
      phases of the disease. Cell surface phenotype was assessed by two- and 
      three-color flow cytometry, and function was determined in vitro by nitric oxide 
      (NO) production, with or without further cytokine stimulation or by 
      immunohistochemistry to determine expression of beta-glucuronidase, nitric oxide 
      synthase (NOS)-2, and nitrotyrosine. RESULTS: Myeloid-derived cells from normal 
      retina were programmed similar to TGF-beta-stimulated uncommitted 
      bone-marrow-derived macrophages (BMDMs). Contrary to BMDM behavior, 
      retina-isolated macrophages displayed distinct properties and phenotype at 
      different phases of the disease course and remained resistant throughout, to 
      further cytokine challenge in vitro. During peak disease, retina-isolated 
      macrophages had characteristics of IFN-gamma/TNF-alpha primed cells 
      (nitrotyrosine positive and NO producing). Despite equivalent numbers of 
      macrophages during resolution, their function reverted to characteristics of 
      TGF-beta primed cells (beta-glucuronidase positive). CONCLUSIONS: Resident 
      retinal myeloid-derived cells are primed and are resistant to further cytokine 
      stimulation, and, similar to macrophages derived during EAU recovery, behave 
      operationally as though TGF-beta primed. During peak inflammation, infiltrating 
      macrophages adapt to concurrent hierarchical Th1 T-cell response 
      (IFN-gamma/TNF-alpha), generating NO. The results provide evidence of in vivo 
      programming of macrophages within the retina.
FAU - Robertson, Morag J
AU  - Robertson MJ
AD  - Department of Ophthalmology, University of Aberdeen, Aberdeen, Scotland, UK.
FAU - Erwig, Lars P
AU  - Erwig LP
FAU - Liversidge, Janet
AU  - Liversidge J
FAU - Forrester, John V
AU  - Forrester JV
FAU - Rees, Andrew J
AU  - Rees AJ
FAU - Dick, Andrew D
AU  - Dick AD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Cytokines)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 3604-79-3 (3-nitrotyrosine)
RN  - 42HK56048U (Tyrosine)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, rat)
RN  - EC 3.2.1.31 (Glucuronidase)
SB  - IM
MH  - Animals
MH  - Autoimmune Diseases/chemically induced/*immunology/pathology
MH  - Cytokines/pharmacology
MH  - Female
MH  - Flow Cytometry
MH  - Fluorescent Antibody Technique, Indirect
MH  - Glucuronidase/metabolism
MH  - Immunoenzyme Techniques
MH  - Immunophenotyping
MH  - Macrophage Activation/*physiology
MH  - Macrophages/drug effects/*physiology
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase/metabolism
MH  - Nitric Oxide Synthase Type II
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Retina/*immunology
MH  - Retinitis/chemically induced/*immunology/pathology
MH  - Tyrosine/*analogs & derivatives/metabolism
MH  - Uveitis/chemically induced/*immunology/pathology
EDAT- 2002/07/02 10:00
MHDA- 2002/07/16 10:01
CRDT- 2002/07/02 10:00
PHST- 2002/07/02 10:00 [pubmed]
PHST- 2002/07/16 10:01 [medline]
PHST- 2002/07/02 10:00 [entrez]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2002 Jul;43(7):2250-7.