Identification and characterization of infiltrating macrophages in acetaminophen-induced liver injury
Identification and characterization of infiltrating macrophages in acetaminophen-induced liver injury
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DOI：
10.1189/jlb.0308173
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发表时间：
2008-12-01
影响因子：
5.5
通讯作者：
Ju, Cynthia
中科院分区：
文献类型：
--
作者：
Holt, Michael P.;Cheng, LinLing;Ju, Cynthia
巨噬细胞在对乙酰氨基酚（APAP）诱导的肝损伤发病机制中的作用仍然存在争议，因为已经证明这些细胞具有促毒性和肝保护功能。这种争议可能源于巨噬细胞的异质性和/或可塑性，以及在肝脏中区分和差异研究巨噬细胞亚群的困难。在本研究中，利用流式细胞分析和针对特定细胞表面巨噬细胞标记的荧光标记抗体，我们能够首次鉴定出apap诱导的巨噬细胞（IM）群体与常驻Kupffer细胞不同。数据表明，IMs来源于apap诱导的肝损伤后浸润肝脏的循环单核细胞。IMs表现出与选择性活化巨噬细胞一致的表型，并表现出吞噬凋亡细胞和诱导中性粒细胞凋亡的能力。此外，在缺乏IMs的情况下，与野生型小鼠相比，CCR2（-/-）小鼠apap诱导的肝毒性后肝损伤的消退延迟。这些发现可能有助于IMs在组织修复过程中的作用，包括对抗炎症和促进血管生成。本研究还证明了分离巨噬细胞群的能力，并在肝脏和其他组织的炎症疾病的未来研究中描述了每组巨噬细胞的不同功能。j . Leukoc。生物学报84:1410-1421；2008.
The role of macrophages in the pathogenesis of acetaminophen (APAP)-induced liver injury remains controversial, as it has been demonstrated that these cells display pro-toxicant and hepato-protective functions. This controversy may stem from the heterogeneity and/or plasticity of macrophages and the difficulty in distinguishing and differentially studying subpopulations of macrophages in the liver. In the present study, using flow cytometric analysis and fluorescence-labeled antibodies against specific cell surface macrophage markers, we were able to, for the first time, identify an APAP-induced macrophage (IM) population distinct from resident Kupffer cells. The data demonstrated that the IMs were derived from circulating monocytes that infiltrated the liver following APAP-induced liver injury. The IMs exhibited a phenotype consistent with that of alternatively activated macrophages and demonstrated the ability to phagocytize apoptotic cells and induce apoptosis of neutrophils. Furthermore, in the absence of the IMs, the resolution of hepatic damage following APAP-induced hepatotoxicity was delayed in CCR2(-/-) mice compared with wild-type mice. These findings likely contribute to the role of the IMs in the processes of tissue repair, including counteracting inflammation and promoting angiogenesis. The present study also demonstrated the ability of separating populations of macrophages and delineating distinct functions of each group in future studies of inflammatory disease in the liver and other tissues. J. Leukoc. Biol. 84: 1410-1421; 2008.