巨噬细胞耗竭及其在肝损伤中的应用

于倩; 赵赛; 刘亮明

doi:10.3969/j.issn.1001-5256.2022.12.034

巨噬细胞耗竭及其在肝损伤中的应用

DOI: 10.3969/j.issn.1001-5256.2022.12.034

南京医科大学上海松江临床医学院，上海 201615

基金项目:

国家自然科学基金 (81770612)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：于倩负责收集整合文献资料以及撰写论文；赵赛负责收集文献；刘亮明对确定写作思路及框架具有关键贡献，并且参与指导撰写、修改论文以及文章最终定稿。

详细信息

通信作者:
刘亮明，liuliangming@hotmail.com

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出版历程
- 收稿日期: 2022-04-20
- 录用日期: 2022-05-21
- 出版日期: 2022-12-20

Macrophage depletion and its application in liver injury

Songjiang Hospital Affiliated to Nanjing Medical University, Shanghai 201615, China

Research funding:

National Natural Science Foundation of China (81770612)

More Information

Corresponding author: LIU Liangming, liuliangming@hotmail.com (ORCID: 0000-0001-6001-8729)

摘要

摘要: 巨噬细胞是一种异质性细胞群，参与组织稳态、炎症和各种病理生理过程。巨噬细胞选择性地体内清除是一种被广泛接受的方法，用于研究巨噬细胞是否参与任何特定的生物学调控机制。了解不同巨噬细胞耗竭的方法及原理有助于探索研究巨噬细胞和疾病关系的合适的建模方案。肝巨噬细胞在肝毒性中起着至关重要的作用。本文就巨噬细胞耗竭的方法及巨噬细胞耗竭后在肝损伤和修复中的调节作用进行综述。
- 枯否细胞 /
- 巨噬细胞 /
- 肝损伤
Abstract: Macrophages are a heterogeneous cell population involved in tissue homeostasis, inflammation, and various pathophysiological processes. Selective clearance of macrophages in vivo is a widely accepted method used to investigate whether macrophages are involved in any specific biological regulatory mechanism. Understanding the different methods and principles of macrophage depletion helps explore appropriate modeling solutions to investigate the relationship between macrophages and diseases. Hepatic macrophages play a crucial role in hepatotoxicity. This article reviews the methods of macrophage depletion and the regulatory role of macrophage depletion in liver injury and repair.
- Kupffer Cells /
- Macrophage /
- Liver Injury

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图 1 巨噬细胞耗竭的肝保护作用机制

注：LncRNA-H19，长链非编码RNA-H19；MMP-12，基质金属蛋白酶-12。

Figure 1. Liver protective mechanisms of macrophage depletion

下载: 全尺寸图片幻灯片

参考文献(49)

[1]	刘梦琪, 臧奕, 李佳. 肝脏巨噬细胞在组织稳态和肝脏疾病中的功能探讨[J]. 药学进展, 2018, 42(10): 723-736. DOI: CNKI:SUN:YXJZ.0.2018-10-003. LIU MQ, ZANG Y, LI J. The roles of hepatic macrophages in tissue homeostasis and liver diseases[J]. Progr Pharm Sci, 2018, 42 (10): 723-736. DOI: CNKI:SUN:YXJZ.0.2018-10-003.
[2]	KAMBARA K, OHASHI W, TOMITA K, et al. In vivo depletion of CD206+ M2 macrophages exaggerates lung injury in endotoxemic mice[J]. Am J Pathol, 2015, 185(1): 162-171. DOI: 10.1016/j.ajpath.2014.09.005.
[3]	SLEGERS TP, TORRES PF, BROERSMA L, et al. Effect of macrophage depletion on immune effector mechanisms during corneal allograft rejection in rats[J]. Invest Ophthalmol Vis Sci, 2000, 41(8): 2239-2247.
[4]	OGUMA K, OSHIMA H, AOKI M, et al. Activated macrophages promote Wnt signalling through tumour necrosis factor-alpha in gastric tumour cells[J]. EMBO J, 2008, 27(12): 1671-1681. DOI: 10.1038/emboj.2008.105.
[5]	LIAO X, CHANG E, TANG X, et al. Cardiac macrophages regulate isoproterenol-induced Takotsubo-like cardiomyopathy[J]. JCI Insight, 2022, 7(3): e156236. DOI: 10.1172/jci.insight.156236.
[6]	JI K, FAN M, HUANG D, et al. Clodronate-nintedanib-loaded exosome-liposome hybridization enhances the liver fibrosis therapy by inhibiting Kupffer cell activity[J]. Biomater Sci, 2022, 10(3): 702-713. DOI: 10.1039/d1bm01663f.
[7]	WEISSIG V. Liposomes: Methods and Protocols, Volume 1: Pharmaceutical Nanocarriers[M]. Humana Press, 2010: 605.
[8]	ESPINOSA-HEIDMANN DG, SUNER IJ, HERNANDEZ EP, et al. Macrophage depletion diminishes lesion size and severity in experimental choroidal neovascularization[J]. Invest Ophthalmol Vis Sci, 2003, 44(8): 3586-3592. DOI: 10.1167/iovs.03-0038.
[9]	SUN L, FAN M, HUANG D, et al. Clodronate-loaded liposomal and fibroblast-derived exosomal hybrid system for enhanced drug delivery to pulmonary fibrosis[J]. Biomaterials, 2021, 271: 120761. DOI: 10.1016/j.biomaterials.2021.120761.
[10]	LI Q, ZHENG M, LIU Y, et al. A pathogenetic role for M1 macrophages in peritoneal dialysis-associated fibrosis[J]. Mol Immunol, 2018, 94: 131-139. DOI: 10.1016/j.molimm.2017.12.023.
[11]	BADER JE, ENOS RT, VELÁZQUEZ KT, et al. Repeated clodronate-liposome treatment results in neutrophilia and is not effective in limiting obesity-linked metabolic impairments[J]. Am J Physiol Endocrinol Metab, 2019, 316(3): E358-E372. DOI: 10.1152/ajpendo.00438.2018.
[12]	HARSTAD EB, KLAASSEN CD. Gadolinium chloride pretreatment prevents cadmium chloride-induced liver damage in both wild-type and MT-null mice[J]. Toxicol Appl Pharmacol, 2002, 180(3): 178-185. DOI: 10.1006/taap.2002.9385.
[13]	BLOOMER SA, MOYER ED, BROWN KE, et al. Aging results in accumulation of M1 and M2 hepatic macrophages and a differential response to gadolinium chloride[J]. Histochem Cell Biol, 2020, 153(1): 37-48. DOI: 10.1007/s00418-019-01827-y.
[14]	ZENG TS, LIU FM, ZHOU J, et al. Depletion of Kupffer cells attenuates systemic insulin resistance, inflammation and improves liver autophagy in high-fat diet fed mice[J]. Endocr J, 2015, 62(7): 615-626. DOI: 10.1507/endocrj.EJ15-0046.
[15]	GUO Z, CHEN J, ZENG Y, et al. Complement inhibition alleviates cholestatic liver injury through mediating macrophage infiltration and function in mice[J]. Front Immunol, 2021, 12: 785287. DOI: 10.3389/fimmu.2021.785287.
[16]	DU C, WANG P, YU Y, et al. Gadolinium chloride improves the course of TNBS and DSS-induced colitis through protecting against colonic mucosal inflammation[J]. Sci Rep, 2014, 4: 6096. DOI: 10.1038/srep06096.
[17]	MUN SH, BAE S, ZENG S, et al. Augmenting MNK1/2 activation by c-FMS proteolysis promotes osteoclastogenesis and arthritic bone erosion[J]. Bone Res, 2021, 9(1): 45. DOI: 10.1038/s41413-021-00162-0.
[18]	IVANOV S, GALLERAND A, GROS M, et al. Mesothelial cell CSF1 sustains peritoneal macrophage proliferation[J]. Eur J Immunol, 2019, 49(11): 2012-2018. DOI: 10.1002/eji.201948164.
[19]	RYAN GR, DAI XM, DOMINGUEZ MG, et al. Rescue of the colony-stimulating factor 1 (CSF-1)-nullizygous mouse (Csf1(op)/Csf1(op)) phenotype with a CSF-1 transgene and identification of sites of local CSF-1 synthesis[J]. Blood, 2001, 98(1): 74-84. DOI: 10.1182/blood.v98.1.74.
[20]	BONNARDEL J, T'JONCK W, GAUBLOMME D, et al. Stellate cells, hepatocytes, and endothelial cells imprint the kupffer cell identity on monocytes colonizing the liver macrophage niche[J]. Immunity, 2019, 51(4): 638-654. e9. DOI: 10.1016/j.immuni.2019.08.017.
[21]	SOTO-DIAZ K, VAILATI-RIBONI M, LOUIE AY, et al. Treatment with the CSF1R antagonist GW2580, sensitizes microglia to reactive oxygen species[J]. Front Immunol, 2021, 12: 734349. DOI: 10.3389/fimmu.2021.734349.
[22]	CHALMERS SA, CHITU V, HERLITZ LC, et al. Macrophage depletion ameliorates nephritis induced by pathogenic antibodies[J]. J Autoimmun, 2015, 57: 42-52. DOI: 10.1016/j.jaut.2014.11.007.
[23]	MURRAY LJ, ABRAMS TJ, LONG KR, et al. SU11248 inhibits tumor growth and CSF-1R-dependent osteolysis in an experimental breast cancer bone metastasis model[J]. Clin Exp Metastasis, 2003, 20(8): 757-766. DOI: 10.1023/b:clin.0000006873.65590.68.
[24]	PATWARDHAN PP, SURRIGA O, BECKMAN MJ, et al. Sustained inhibition of receptor tyrosine kinases and macrophage depletion by PLX3397 and rapamycin as a potential new approach for the treatment of MPNSTs[J]. Clin Cancer Res, 2014, 20(12): 3146-3158. DOI: 10.1158/1078-0432.CCR-13-2576.
[25]	YAMAMOTO T, KAIZU C, KAWASAKI T, et al. Macrophage colony-stimulating factor is indispensable for repopulation and differentiation of Kupffer cells but not for splenic red pulp macrophages in osteopetrotic (op/op) mice after macrophage depletion[J]. Cell Tissue Res, 2008, 332(2): 245-256. DOI: 10.1007/s00441-008-0586-8.
[26]	STANLEY ER, CHITU V. CSF-1 receptor signaling in myeloid cells[J]. Cold Spring Harb Perspect Biol, 2014, 6(6): a021857. DOI: 10.1101/cshperspect.a021857.
[27]	DAI XM, RYAN GR, HAPEL AJ, et al. Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects[J]. Blood, 2002, 99(1): 111-120. DOI: 10.1182/blood.v99.1.111.
[28]	CIPRIANI G, GIBBONS SJ, MILLER KE, et al. Change in populations of macrophages promotes development of delayed gastric emptying in mice[J]. Gastroenterology, 2018, 154(8): 2122-2136. e12. DOI: 10.1053/j.gastro.2018.02.027.
[29]	TARIQ M, ZHANG JQ, LIANG GK, et al. Gefitinib inhibits M2-like polarization of tumor-associated macrophages in Lewis lung cancer by targeting the STAT6 signaling pathway[J]. Acta Pharmacol Sin, 2017, 38(11): 1501-1511. DOI: 10.1038/aps.2017.124.
[30]	KADONO K, KAGEYAMA S, NAKAMURA K, et al. Myeloid Ikaros-SIRT1 signaling axis regulates hepatic inflammation and pyroptosis in ischemia-stressed mouse and human liver[J]. J Hepatol, 2022, 76(4): 896-909. DOI: 10.1016/j.jhep.2021.11.026.
[31]	LAVIN Y, WINTER D, BLECHER-GONEN R, et al. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment[J]. Cell, 2014, 159(6): 1312-1326. DOI: 10.1016/j.cell.2014.11.018.
[32]	SCOTT CL, ZHENG F, de BAETSELIER P, et al. Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells[J]. Nat Commun, 2016, 7: 10321. DOI: 10.1038/ncomms10321.
[33]	CHAKAROV S, LIM HY, TAN L, et al. Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches[J]. Science, 2019, 363(6432): eaau0964. DOI: 10.1126/science.aau0964.
[34]	SUZUKI Y, SHIRAI M, ASADA K, et al. Macrophage mannose receptor, CD206, predict prognosis in patients with pulmonary tuberculosis[J]. Sci Rep, 2018, 8(1): 13129. DOI: 10.1038/s41598-018-31565-5.
[35]	STEEL CD, STEPHENS AL, HAHTO SM, et al. Comparison of the lateral tail vein and the retro-orbital venous sinus as routes of intravenous drug delivery in a transgenic mouse model[J]. Lab Anim (NY), 2008, 37(1): 26-32. DOI: 10.1038/laban0108-26.
[36]	BURNETT SH, KERSHEN EJ, ZHANG J, et al. Conditional macrophage ablation in transgenic mice expressing a Fas-based suicide gene[J]. J Leukoc Biol, 2004, 75(4): 612-623. DOI: 10.1189/jlb.0903442.
[37]	YU X, LIU H, HAMEL KA, et al. Dorsal root ganglion macrophages contribute to both the initiation and persistence of neuropathic pain[J]. Nat Commun, 2020, 11(1): 264. DOI: 10.1038/s41467-019-13839-2.
[38]	BANK RA, ZANDSTRA J, ROOM H, et al. Biomaterial encapsulation is enhanced in the early stages of the foreign body reaction during conditional macrophage depletion in transgenic macrophage fas-induced apoptosis mice[J]. Tissue Eng Part A, 2017, 23(19-20): 1078-1087. DOI: 10.1089/ten.TEA.2016.0499.
[39]	BAILEY KN, FURMAN BD, ZEITLIN J, et al. Intra-articular depletion of macrophages increases acute synovitis and alters macrophage polarity in the injured mouse knee[J]. Osteoarthritis Cartilage, 2020, 28(5): 626-638. DOI: 10.1016/j.joca.2020.01.015.
[40]	SCHVMANN J, WOLF D, PAHL A, et al. Importance of Kupffer cells for T-cell-dependent liver injury in mice[J]. Am J Pathol, 2000, 157(5): 1671-1683. DOI: 10.1016/S0002-9440(10)64804-3.
[41]	GIAKOUSTIDIS D, PAPAGEORGIOU G, ILIADIS S, et al. The protective effect of alpha-tocopherol and GdCl3 against hepatic ischemia/reperfusion injury[J]. Surg Today, 2006, 36(5): 450-456. DOI: 10.1007/s00595-005-3162-9.
[42]	ZHANG W, ZHU X, TANG Y, et al. Kupffer cells depletion alters cytokine expression and delays liver regeneration after radio-frequency-assisted liver partition with portal vein ligation[J]. Mol Immunol, 2022, 144: 71-77. DOI: 10.1016/j.molimm.2022.02.016.
[43]	JIAO J, SASTRE D, FIEL MI, et al. Dendritic cell regulation of carbon tetrachloride-induced murine liver fibrosis regression[J]. Hepatology, 2012, 55(1): 244-255. DOI: 10.1002/hep.24621.
[44]	TIAN X, WANG Y, LU Y, et al. Conditional depletion of macrophages ameliorates cholestatic liver injury and fibrosis via lncRNA-H19[J]. Cell Death Dis, 2021, 12(7): 646. DOI: 10.1038/s41419-021-03931-1.
[45]	PRADERE JP, KLUWE J, de MINICIS S, et al. Hepatic macrophages but not dendritic cells contribute to liver fibrosis by promoting the survival of activated hepatic stellate cells in mice[J]. Hepatology, 2013, 58(4): 1461-1473. DOI: 10.1002/hep.26429.
[46]	PELLICORO A, AUCOTT RL, RAMACHANDRAN P, et al. Elastin accumulation is regulated at the level of degradation by macrophage metalloelastase (MMP-12) during experimental liver fibrosis[J]. Hepatology, 2012, 55(6): 1965-1975. DOI: 10.1002/hep.25567.
[47]	ZHU F, LI X, JIANG Y, et al. GdCl3 suppresses the malignant potential of hepatocellular carcinoma by inhibiting the expression of CD206 in tumor-associated macrophages[J]. Oncol Rep, 2015, 34(5): 2643-2655. DOI: 10.3892/or.2015.4268.
[48]	YANG X, HE Y, SHI QQ, et al. Effect of in vivo Kupffer cell-targeted gene knockdown with GeRPs on expression of Ces1f in liver tissues of mice with acute liver failure[J]. J Med Mol Biol, 2020, 17(3): 221-227. DOI: 10.3870/j.issn.1672-8009.2020.03.008. 杨雪, 何玉, 施青青, 等. 活体枯否细胞靶向性基因敲减GeRPs方法对急性肝衰竭小鼠肝组织Ces1f基因表达的影响[J]. 医学分子生物学杂志, 2020, 17(3): 221-227. DOI: 10.3870/j.issn.1672-8009.2020.03.008.
[49]	GABRUSIEWICZ K, HOSSAIN MB, CORTES-SANTIAGO N, et al. Macrophage ablation reduces M2-like populations and jeopardizes tumor growth in a MAFIA-based glioma model[J]. Neoplasia, 2015, 17(4): 374-384. DOI: 10.1016/j.neo.2015.03.003.