期刊
PLOS ONE
卷 11, 期 9, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0162286
关键词
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资金
- Brustem: Impulse program (Brussels Government) [2011-IP-LS-104-Brustem]
- Flemish Government Agency for Innovation by Science and Technology [IWT/SB/121548]
- Interuniversity Attraction Poles (IAP)-phase VII (Federal Science Policy-BELSPO) [P7/47]
- Research Foundation Flanders (FWO) [G.0333.13N]
- Foundation for Liver Research, UK
- Deutsche Forschungsgemeinschaft (DFG) [267/4-1, 267/6-1, 267/8-1]
- Wilhelm Laupitz Foundation
- NICHD
- [FWO G.0348.13N]
Chronic cholangiopathies, such as primary and secondary sclerosing cholangitis, are progressive disease entities, associated with periportal accumulation of inflammatory cells, encompassing monocytes and macrophages, peribiliary extracellular matrix (ECM) deposition and ductular reaction (DR). This study aimed to elucidate the relevance of macrophages in the progression of chronic cholangiopathies through macrophage depletion in a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) mouse model. One group of mice received a single i.p. injection of Clodronate encapsulated liposomes (CLOLipo) at day 7 of a 14 day DDC treatment, while control animals were co-treated with PBSLipo instead. Mice were sacrificed after 7 or respectively 14 days of treatment for immunohistochemical assessment of macrophage recruitment (F4/80), ECM deposition (Sirius Red, Laminin) and DR (CK19). Macrophage depletion during a 14 day DDC treatment resulted in a significant inhibition of ECM deposition. Porto-lobular migration patterns of laminin-rich ECM and ductular structures were significantly attenuated and a progression of DR was effectively inhibited by macrophage depletion. CLOLipo co-treatment resulted in a confined DR to portal regions without amorphous cell clusters. This study suggests that therapeutic options selectively directed towards macrophages might represent a feasible treatment for chronic cholestatic liver diseases.
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