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J. B. Self-Fordham, L. B. Nicholson, A. D. Dick; Diversity in Thrombospondin-1 Expression Patterns by Murine Macrophages. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5928.
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To elucidate the regulatory mechanisms that control TSP-1 expression by macrophages.
Bone-Marrow derived Macrophages (BM-MΦ) and Peritoneal Macrophages (P.MΦ) were prepared from CD57BL/6 and TSP-1 -/- mice and stimulated under various conditions in vitro. TSP-1 expression was then detected by FACS analysis and nitrite (NO) production quantified using Griess regeant.
Stimulation with LPS resulted in upregulation of TSP-1 expression by BM-MΦs, an effect that was greater in P.MΦs. IFN-γ alone, but not in conjunction with LPS, down-regulated TSP-1 expression by BM.MΦs, an effect that was absent in P.MΦs. LPS also induced NO production in BM-MΦs and TSP-1 -/- cells displayed a deficit compared to WT cells. P.MΦs did not respond to LPS alone, however the addition of IFN-γ restored their NO response. Again, under these conditions TSP-1 -/- cells displayed a deficit compared to WT, and this deficit was greater than the one observed in BM-MΦs.Conclusion: TSP-1 expression by MΦs is known to influence their role in inflammation and immune responses in several ways, including NO production in response to cytokines and innate stimuli. MΦs display significant plasticity in their pattern of TSP-1 expression in response to these stimuli; as BM-MΦs and P.MΦs, which have significant differences in their environmental conditions prior to stimulation in vitro, display distinct patterns of expression.
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