Macrophage Depletion Attenuates Extracellular Matrix Deposition and Ductular Reaction in a Mouse Model of Chronic Cholangiopathies.
Macrophage Depletion Attenuates Extracellular Matrix Deposition and Ductular Reaction in a Mouse Model of Chronic Cholangiopathies.
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DOI：
10.1371/journal.pone.0162286
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
van Grunsven LA
中科院分区：
文献类型：
--
作者：
Best J;Verhulst S;Syn WK;Lagaisse K;van Hul N;Heindryckx F;Sowa JP;Peeters L;Van Vlierberghe H;Leclercq IA;Canbay A;Dollé L;van Grunsven LA
慢性胆管病，例如原发性和继发性硬化性胆管炎，是进行性疾病实体，与炎性细胞（包括单核细胞和巨噬细胞）的汇管周围积聚、胆管周围细胞外基质（ECM）沉积和导管反应（DR）相关。本研究旨在通过 3,5-二乙氧基羰基-1,4-二氢可力丁 (DDC) 小鼠模型中巨噬细胞耗竭来阐明巨噬细胞在慢性胆管病进展中的相关性。一组小鼠接受单次腹腔注射。在 14 天的 DDC 治疗的第 7 天注射氯膦酸盐封装的脂质体 (CLOLipo)，而对照动物则用 PBSLipo 共同治疗。治疗7天或14天后处死小鼠，对巨噬细胞募集（F4/80）、ECM沉积（天狼星红、层粘连蛋白）和DR（CK19）进行免疫组织化学评估。 14 天的 DDC 治疗期间巨噬细胞的消耗导致 ECM 沉积的显着抑制。富含层粘连蛋白的 ECM 和导管结构的门小叶迁移模式显着减弱，巨噬细胞耗竭有效抑制了 DR 的进展。 CLOLipo 共处理导致 DR 局限于汇管区，没有无定形细胞簇。这项研究表明，选择性针对巨噬细胞的治疗方案可能代表慢性胆汁淤积性肝病的可行治疗方法。
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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影响因子：
82.9
作者：
通讯作者：
--
影响因子：
6
作者：
Fickert, Peter;Stoeger, Ulrike;Trauner, Michael
通讯作者：
Trauner, Michael
影响因子：
5.1
作者：
Hirschfield, Gideon M.
通讯作者：
Hirschfield, Gideon M.
影响因子：
3.2
作者：
Lazaridis, Konstantinos N.
通讯作者：
Lazaridis, Konstantinos N.
影响因子：
24.5
作者：
Lorenzini S;Bird TG;Boulter L;Bellamy C;Samuel K;Aucott R;Clayton E;Andreone P;Bernardi M;Golding M;Alison MR;Iredale JP;Forbes SJ
通讯作者：
Forbes SJ