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D. Banerjee, J.D. Sedgwick, S. Nicholls, A.D. Dick; Lacking CD200 Does Not Impair Macrophage Ability to Respond to TGFbeta Despite Activation and High Nitrite Production in Steady-state . Invest. Ophthalmol. Vis. Sci. 2003;44(13):725.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:: Macrophage activation and conditioning during inflammation is dependent upon initial cytokine stimulation. Recent evidence of cognate suppression of macrophage activation via the CD200 receptor (CD200R) following CD200 engagement is supported by studies in CD200KO mice which display increased susceptibility to and early onset of experimental autoimmunity. We therefore wished to investigate if in the absence of CD200, macrophages remain responsive to further cytokine programming, which may be adapted therapeutically to suppress tissue damage. Methods: Experimental autoimmune uveoretinitits (EAU) was induced in CD200-/- (KO) and C57BL/6 Wild type (WT) mice following immunisation with IRBP-1-20 peptide with adjuvant. At days 15,25,32 post immunisation, retinal macrophages were isolated and function and ability to respond to cytokines was assessed via nitrite production, NOS2 expression and ß-glucuronidase expression with or without further cytokine stimulation in vitro. Results: In the absence of CD200, retinal macrophages have increased nitrite production, but nitrite production at height of disease, and their ability to respond to IFNγ and TNF-mediated nitrite production is reduced compared to WT. In KO mice, macrophages still respond to TGFß-mediated suppression of nitrite production and are enabled to express ß-glucuronidase during resolution of disease. Conclusions: Loss of CD200 expression releases tonic macrophage suppression, as seen by increased NOS2 and nitrite production in the steady state, but macrophages do not respond to further cytokine-mediated nitrite production. CD200 did not regulate TGFß-mediated macrophage conditioning which may explain the ability to resolve inflammation despite constitutive macrophage activation.
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