Contrasting responses of Kupffer cells and inflammatory mononuclear phagocytes to biliary obstruction in a mouse model of cholestatic liver injury.
Contrasting responses of Kupffer cells and inflammatory mononuclear phagocytes to biliary obstruction in a mouse model of cholestatic liver injury.
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DOI：
10.1111/liv.12048
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发表时间：
2013-02
期刊：
影响因子：
--
通讯作者：
Gregory SH
中科院分区：
文献类型：
--
作者：
Duwaerts CC;Gehring S;Cheng CW;van Rooijen N;Gregory SH
胆道梗阻和胆汁淤积是许多肝脏疾病的严重并发症。虽然常驻肝巨噬细胞（库普弗细胞）经常与疾病进展有关，但大多数研究未能区分库普弗细胞和阻塞后浸润肝脏的炎症性单核吞噬细胞（iMNP）的贡献。本研究的目的是检查这两种不同的单核吞噬细胞群在伴有胆汁淤积的肝损伤中的作用和潜在的相互作用。雌性 C57Bl/6 小鼠在假手术或胆管结扎 (BDL) 前第三天注射磁珠，以促进随后的库普弗细胞分离。手术三天后，对动物实施安乐死，并分离、纯化和分析含有珠子的 Kupffer 细胞和 iMNP。为了检查 Kupffer 细胞调节 iMNP 活性的能力，在术后第 3 天从完整小鼠和 Kupffer 细胞耗尽小鼠的肝脏中分离 iMNP 并进行比较。从 BDL 小鼠获得的纯化 Kupffer 细胞和 iMNP 群体表现出异质形态，使它们在视觉上无法区分。然而，iMNP 的特点是 Ly-6C 和 CD11b 的表达增加以及炎症细胞特征的趋化因子/细胞因子的产生增加。在缺乏库普弗细胞的情况下，BDL 后迁移至肝脏的 iMNP 表现出 CD11b 和 Ly-6C 表达以及促炎趋化因子/细胞因子产生的显着降低。库普弗细胞和 iMNP 对胆道梗阻和胆汁淤积表现出不同的生物反应。库普弗细胞在调节 iMNP 流入和活性中发挥着关键作用。
Biliary obstruction and cholestasis are serious complications of many liver diseases. While resident hepatic macrophages (Kupffer cells) are frequently implicated in disease progression, most studies fail to differentiate the contribution of Kupffer cells and inflammatory mononuclear phagocytes (iMNPs) that infiltrate the liver subsequent to obstruction. This study was undertaken to examine the roles and potential interactions of these two disparate mononuclear phagocyte populations in hepatic injury attending cholestasis. Female, C57Bl/6 mice were injected with magnetic beads on day three prior to sham operation or bile duct ligation (BDL) in order to facilitate subsequent Kupffer cell isolation. Three days post surgery, animals were euthanized, and bead-containing Kupffer cells and iMNPs were separated, purified, and analyzed. To examine the ability of Kupffer cells to modulate iMNP activity, iMNPs were isolated from the livers of intact and Kupffer cell-depleted mice on day 3 post-surgery and compared. Purified Kupffer cells and iMNP populations obtained from BDL mice exhibited heterogeneous morphologies rendering them visually indistinguishable. iMNPs, however, were characterized by the increased expression of Ly-6C and CD11b and the elevated production of chemokines/cytokines characteristic of inflammatory cells. In the absence of Kupffer cells, iMNPs immigrating to the liver following BDL exhibited significant decreases in CD11b and Ly-6C expression, and in pro-inflammatory chemokine/cytokine production. Kupffer cells and iMNPs exhibit disparate biological responses to biliary obstruction and cholestasis. Kupffer cells play a key role in regulating iMNP influx and activity.
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DOI：
10.1084/jem.148.1.1
发表时间：
1978-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Crofton RW;Diesselhoff-den Dulk MM;van Furth R
通讯作者：
van Furth R
影响因子：
3.2
作者：
Chavez, Enrique;Alcantar, Lidia K.;Muriel, Pablo
通讯作者：
Muriel, Pablo
影响因子：
15.9
作者：
Fadok, VA;Bratton, DL;Henson, PM
通讯作者：
Henson, PM
影响因子：
3.8
作者：
Jaeschke, H;Gores, GJ;Lemasters, JJ
通讯作者：
Lemasters, JJ
DOI：
10.1073/pnas.88.3.1044
发表时间：
1991-02-01
影响因子：
11.1
作者：
LOIKE, JD;SODEIK, B;SILVERSTEIN, SC
通讯作者：
SILVERSTEIN, SC