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Amniotic membrane induces Peroxisome Proliferator-Activated Receptor γ positive alternatively activated macrophages.
MedLine Citation:
PMID:  22222510     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Purpose:Amniotic membrane transplantation (AMT) reportedly improves herpetic stromal keratitis (HSK). Here we studied the role of the AM on macrophages.Methods:BALB/c mice with necrotizing HSK received an AMT or tarsorrhaphy (TAR) as control. Apoptosis of F4/80+cells was determined using the annexinV/7-AAD system. Macrophage invasion was determined by using a cornea invasion assay. Cytokine secretion was quantified by ELISA. Arginase activity was measured by bioassay. Expression of NFĸB or PPAR-γ related proteins was detected by western blot, and the expression of costimulatory surface molecules or PPAR-γ by flow cytometry. Lipid accumulation was observed by Oil red O and Sudan B staining.Results:After AMT apoptotic features of corneal macrophages, but also macrophage invasion increased. IL-6, IL-10, IL-12, TNF-α, and NF-ĸB content in HSK corneas had decreased with AMT. AMT increased expression of PPAR-γ, arginase 1+2, and arginase activity in AM treated HSK corneas. In vitro, NF-kB, cytokine production, costimulatory molecules (CD80, CD86, CD40), phagocytic capacity, proliferation, viability, and accessory function to HSV-1 specific DLN cells where reduced in BM cocultured with AM, while CD206, CD204, CD163, CD68, lipid accumulation in the cytoplasm, PPAR-γ expression, and arginase activity was increased.An increase in viability and proliferation was observed in the presence of AM combined with apoptotic cells, as compared to AM alone.Conclusions:We conclude that the action mechanism of AM is associated with modulation of classically activated macrophages into alternatively activated macrophages or macrophage cell death, probably by engaging lipid metabolism and activating the PPAR-γ pathway, consequently curtailing effector T cell functions. Apoptotic cells induced in the environment with AM support the presence and survival of such macrophages.
Authors:
Dirk Bauer; Maren Hennig; Susanne Wasmuth; Hanna Baehler; Martin Busch; Klaus-Peter Steuhl; Solon Thanos; Arnd Heiligenhaus
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-5
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  -     ISSN:  1552-5783     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Ophthalmology and Ophtha-Lab at St. Franziskus Hospital, Muenster, Germany.
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