Role of galectin-3 in classical and alternative macrophage activation in the liver following acetaminophen intoxication.
Role of galectin-3 in classical and alternative macrophage activation in the liver following acetaminophen intoxication.
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DOI：
10.4049/jimmunol.1201851
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发表时间：
2012-12-15
期刊：
影响因子：
--
通讯作者：
Laskin DL
中科院分区：
文献类型：
--
作者：
Dragomir AC;Sun R;Choi H;Laskin JD;Laskin DL
炎性巨噬细胞与镇痛药对乙酰氨基酚（APAP）引起的肝毒性有关。在这些研究中，我们描述了APAP中毒后巨噬细胞在肝脏中积累的表型，并评估了半乳糖凝集素-3 （Gal-3）在巨噬细胞激活中的作用。给野生型小鼠注射APAP （300 mg/kg, i.p）导致肝脏中出现两个不同的CD11b+细胞亚群，表达高或低水平的单核细胞/巨噬细胞激活标记物Ly6C。CD11b+/Ly6Chi巨噬细胞表现出典型激活的促炎表型，其特征是TNF-α、诱导型一氧化氮合酶（iNOS）和CCR2的表达增加，而CD11b+/Ly6Clo巨噬细胞被选择性激活，表达高水平的抗炎细胞因子IL-10。APAP中毒还与肝脏中Gal-3+巨噬细胞的积累有关；这些细胞以Ly6Chi为主。在Gal-3−/−小鼠中，apap诱导的CD11b+/Ly6Chi巨噬细胞的增加明显减少。这在apap后72 h表现明显，并与经典巨噬细胞活化标志物iNOS、IL-12和TNF-α以及促炎趋化因子CCL2和CCL3以及趋化因子受体CCR1和CCR2的表达降低有关。相反，apap处理的Gal-3−/−小鼠肝脏中CD11b+/Ly6Clo巨噬细胞数量增加。这与巨噬细胞激活标志物Ym1和Fizz1的表达增加、肝脏修复增加和肝毒性降低有关。这些数据表明，经典活化和选择性活化的巨噬细胞在APAP中毒后在肝脏中积聚；此外，Gal-3在促进持续的促炎巨噬细胞表型中发挥作用。
Inflammatory macrophages have been implicated in hepatotoxicity induced by the analgesic, acetaminophen (APAP). In these studies we characterized the phenotype of macrophages accumulating in the liver following APAP intoxication and evaluated the role of galectin-3 (Gal-3) in macrophage activation. Administration of APAP (300 mg/kg, i.p.) to wild type mice resulted in the appearance of two distinct subpopulations of CD11b+ cells in the liver, which expressed high or low levels of the monocyte/macrophage activation marker Ly6C. Whereas CD11b+/Ly6Chi macrophages exhibited a classically activated proinflammatory phenotype characterized by increased expression of TNF-α, inducible nitric oxide synthase (iNOS), and CCR2, CD11b+/Ly6Clo macrophages were alternatively activated, expressing high levels of the anti-inflammatory cytokine, IL-10. APAP intoxication was also associated with an accumulation of Gal-3+ macrophages in the liver; the majority of these cells were Ly6Chi. APAP-induced increases in CD11b+/Ly6Chi macrophages were significantly reduced in Gal-3−/− mice. This was evident 72 h post-APAP and was correlated with reduced expression of the classical macrophage activation markers, iNOS, IL-12, and TNF-α, as well as the proinflammatory chemokines, CCL2 and CCL3, and chemokine receptors CCR1, and CCR2. Conversely, numbers of CD11b+/Ly6Clo macrophages increased in livers of APAP-treated Gal-3−/− mice. This was associated with increased expression of the alternative macrophage activation markers Ym1 and Fizz1, increased liver repair and reduced hepatotoxicity. These data demonstrate that both classically and alternatively activated macrophages accumulate in the liver following APAP intoxication; moreover, Gal-3 plays a role in promoting a persistent proinflammatory macrophage phenotype.
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影响因子：
4.1
作者：
Ju, C;Reilly, TP;Pohl, LR
通讯作者：
Pohl, LR
影响因子：
4.4
作者：
Jeon, Sae-Bom;Yoon, Hee Jung;Park, Eun Jung
通讯作者：
Park, Eun Jung
影响因子：
4.1
作者：
Bourdi, Mohammed;Eiras, Daniel P.;Pohl, Lance R.
通讯作者：
Pohl, Lance R.
DOI：
10.1111/j.1749-6632.2009.05131.x
发表时间：
2010-01-01
期刊：
YEAR IN IMMUNOLOGY 2
影响因子：
--
作者：
Liu, Fu-Tong;Rabinovich, Gabriel A.
通讯作者：
Rabinovich, Gabriel A.
影响因子：
13.5
作者：
Bourdi, M;Masubuchi, Y;Pohl, LR
通讯作者：
Pohl, LR