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Cathryn Broderick, Linda Duncan, Neil Taylor, Andrew D. Dick; IFN-γ and LPS-Mediated IL-10–Dependent Suppression of Retinal Microglial Activation. Invest. Ophthalmol. Vis. Sci. 2000;41(9):2613-2622.
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purpose. Human retinal microglia (MG) express constitutively major
histocompatability complex (MHC) class II molecules and have thus been
highlighted as potential immunocompetent antigen-presenting cells
(APCs). This study was undertaken to characterize microglial expression
of coaccessory molecules and the functional changes in antigen
expression, cytokine production, migration, and phagocytosis after
methods. Fresh donor retinal MG were obtained and isolated using a percoll
density gradient technique. Phenotypic characteristics used for
isolating rodent microglia were applied and modified. Coaccessory
molecule expression and intracellular cytokine production were assessed
using three-color flow cytometric analysis in both freshly isolated and
interferon (IFN)γ-lipopolysaccharide (LPS)–stimulated MG. Using
five-millimeter retinal explants in culture, microglial migratory
behavior, changes in cell surface antigen expression and phagocytic
activity were documented.
results. MG could be clearly defined by the flow cytometric phenotype
II+CD86lowCD40low. Freshly isolated
MG showed mannose receptor–mediated uptake of dextran-FITC. MG
migrated from explants, were adherent, and upregulated MHC class II
expression. After IFNγ-LPS stimulation of single-cell suspension of
MG isolates, MHC class II expression was reduced, with an increase
occurring in MG intracellular interleukin (IL)-10 and IL-10 production.
Microglial migration from explants was reduced after IFNγ-LPS
conclusions. These results highlight both phenotypic and behavioral characteristics
that support an antigen-processing and -presenting capability of
freshly isolated MG. However, proinflammatory stimulation with
IFNγ-LPS induces an IL-10–mediated downregulation of cell surface
antigen expression and loss of migratory and phagocytic activity.
Therefore, although equipped to act as APCs, MG are able to rapidly
modulate their own function and behavior and as a result may have the
potential to limit inflammation.
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