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DOI: 10.1055/s-0038-1670674
Regulation of Hepatic Inflammation via Macrophage Cell Death
Funding Work from the author's laboratory was supported by grants R01 AA12863 and R21 AA026025 from the National Institute on Alcohol Abuse and Alcoholism and grant P30 GM118247 from the National Institute of General Medical Sciences.Publikationsverlauf
Publikationsdatum:
24. Oktober 2018 (online)
![](https://www.thieme-connect.de/media/sld/201804/lookinside/thumbnails/10-1055-s-0038-1670674_1800060-1.jpg)
Abstract
Macrophages are innate immune cells with diverse functions including clearing infectious agents, inducing inflammation and fibrosis, resolving fibrosis, and restoring tissue integrity. Liver macrophages consist of both resident Kupffer cells and infiltrating macrophages. They have heterogeneous highly plastic phenotypes, and they change their phenotypes rapidly in response to a diverse array of signals present in the injured or recovering liver. Cell death by apoptosis, necroptosis, or pyroptosis is a common response of liver macrophages to infectious and toxic insults. At the same time, the uptake of apoptotic and other dead cells, efferocytosis, is mediated by a series of dead cell receptors including MerTK, TIM4, and Stablin-1. These generate a critical signal that determines macrophage phenotype evolution. This review discusses the processes that lead to macrophage apoptosis and efferocytosis, and how these alter the course of liver diseases.
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References
- 1 Krenkel O, Tacke F. Liver macrophages in tissue homeostasis and disease. Nat Rev Immunol 2017; 17 (05) 306-321
- 2 Tacke F, Zimmermann HW. Macrophage heterogeneity in liver injury and fibrosis. J Hepatol 2014; 60 (05) 1090-1096
- 3 Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest 2012; 122 (03) 787-795
- 4 Sica A, Invernizzi P, Mantovani A. Macrophage plasticity and polarization in liver homeostasis and pathology. Hepatology 2014; 59 (05) 2034-2042
- 5 Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol 2008; 8 (12) 958-969
- 6 Gordon S. Phagocytosis: an immunobiologic process. Immunity 2016; 44 (03) 463-475
- 7 Elliott MR, Koster KM, Murphy PS. Efferocytosis signaling in the regulation of macrophage inflammatory responses. J Immunol 2017; 198 (04) 1387-1394
- 8 Gordon S, Plüddemann A. Macrophage clearance of apoptotic cells: a critical assessment. Front Immunol 2018; 9: 127
- 9 Seimon T, Tabas I. Mechanisms and consequences of macrophage apoptosis in atherosclerosis. J Lipid Res 2009; 50 (Suppl): S382-S387
- 10 Chow SH, Deo P, Naderer T. Macrophage cell death in microbial infections. Cell Microbiol 2016; 18 (04) 466-474
- 11 Tacke F. Targeting hepatic macrophages to treat liver diseases. J Hepatol 2017; 66 (06) 1300-1312
- 12 Gomez Perdiguero E, Klapproth K, Schulz C. , et al. Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors. Nature 2015; 518 (7540): 547-551
- 13 Mass E, Ballesteros I, Farlik M. , et al. Specification of tissue-resident macrophages during organogenesis. Science 2016; 353 (6304): 353
- 14 Hoeffel G, Chen J, Lavin Y. , et al. C-Myb(+) erythro-myeloid progenitor-derived fetal monocytes give rise to adult tissue-resident macrophages. Immunity 2015; 42 (04) 665-678
- 15 David BA, Rezende RM, Antunes MM. , et al. Combination of mass cytometry and imaging analysis reveals origin, location, and functional repopulation of liver myeloid cells in mice. Gastroenterology 2016; 151 (06) 1176-1191
- 16 Varol C, Mildner A, Jung S. Macrophages: development and tissue specialization. Annu Rev Immunol 2015; 33: 643-675
- 17 Ju C, Tacke F. Hepatic macrophages in homeostasis and liver diseases: from pathogenesis to novel therapeutic strategies. Cell Mol Immunol 2016; 13 (03) 316-327
- 18 Serbina NV, Pamer EG. Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat Immunol 2006; 7 (03) 311-317
- 19 Swirski FK, Nahrendorf M, Etzrodt M. , et al. Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science 2009; 325 (5940): 612-616
- 20 Yona S, Kim KW, Wolf Y. , et al. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity 2013; 38 (01) 79-91
- 21 Schulz C, Gomez Perdiguero E, Chorro L. , et al. A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science 2012; 336 (6077): 86-90
- 22 Dal-Secco D, Wang J, Zeng Z. , et al. A dynamic spectrum of monocytes arising from the in situ reprogramming of CCR2+ monocytes at a site of sterile injury. J Exp Med 2015; 212 (04) 447-456
- 23 Mossanen JC, Krenkel O, Ergen C. , et al. Chemokine (C-C motif) receptor 2-positive monocytes aggravate the early phase of acetaminophen-induced acute liver injury. Hepatology 2016; 64 (05) 1667-1682
- 24 Karlmark KR, Weiskirchen R, Zimmermann HW. , et al. Hepatic recruitment of the inflammatory Gr1+ monocyte subset upon liver injury promotes hepatic fibrosis. Hepatology 2009; 50 (01) 261-274
- 25 Ramachandran P, Pellicoro A, Vernon MA. , et al. Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis. Proc Natl Acad Sci U S A 2012; 109 (46) E3186-E3195
- 26 Wang M, You Q, Lor K, Chen F, Gao B, Ju C. Chronic alcohol ingestion modulates hepatic macrophage populations and functions in mice. J Leukoc Biol 2014; 96 (04) 657-665
- 27 Murray PJ, Allen JE, Biswas SK. , et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 2014; 41 (01) 14-20
- 28 Hamidzadeh K, Christensen SM, Dalby E, Chandrasekaran P, Mosser DM. Macrophages and the recovery from acute and chronic inflammation. Annu Rev Physiol 2017; 79: 567-592
- 29 Vannella KM, Wynn TA. Mechanisms of organ injury and repair by macrophages. Annu Rev Physiol 2017; 79: 593-617
- 30 Sun YY, Li XF, Meng XM, Huang C, Zhang L, Li J. Macrophage phenotype in liver injury and repair. Scand J Immunol 2017; 85 (03) 166-174
- 31 Ritz T, Krenkel O, Tacke F. Dynamic plasticity of macrophage functions in diseased liver. Cell Immunol 2018; 330: 175-182
- 32 Zigmond E, Samia-Grinberg S, Pasmanik-Chor M. , et al. Infiltrating monocyte-derived macrophages and resident Kupffer cells display different ontogeny and functions in acute liver injury. J Immunol 2014; 193 (01) 344-353
- 33 Bernsmeier C, Pop OT, Singanayagam A. , et al. Patients with acute-on-chronic liver failure have increased numbers of regulatory immune cells expressing the receptor tyrosine kinase MERTK. Gastroenterology 2015; 148 (03) 603-615.e14
- 34 Triantafyllou E, Pop OT, Possamai LA. , et al. MerTK expressing hepatic macrophages promote the resolution of inflammation in acute liver failure. Gut 2018; 67 (02) 333-347
- 35 Shapouri-Moghaddam A, Mohammadian S, Vazini H. , et al. Macrophage plasticity, polarization, and function in health and disease. J Cell Physiol 2018; 233 (09) 6425-6440
- 36 Zhou D, Huang C, Lin Z. , et al. Macrophage polarization and function with emphasis on the evolving roles of coordinated regulation of cellular signaling pathways. Cell Signal 2014; 26 (02) 192-197
- 37 Murray PJ. Macrophage Polarization. Annu Rev Physiol 2017; 79: 541-566
- 38 Bosurgi L, Cao YG, Cabeza-Cabrerizo M. , et al. Macrophage function in tissue repair and remodeling requires IL-4 or IL-13 with apoptotic cells. Science 2017; 356 (6342): 1072-1076
- 39 Arandjelovic S, Ravichandran KS. Phagocytosis of apoptotic cells in homeostasis. Nat Immunol 2015; 16 (09) 907-917
- 40 Poon IK, Lucas CD, Rossi AG, Ravichandran KS. Apoptotic cell clearance: basic biology and therapeutic potential. Nat Rev Immunol 2014; 14 (03) 166-180
- 41 Penberthy KK, Ravichandran KS. Apoptotic cell recognition receptors and scavenger receptors. Immunol Rev 2016; 269 (01) 44-59
- 42 Fond AM, Ravichandran KS. Clearance of dying cells by phagocytes: mechanisms and implications for disease pathogenesis. Adv Exp Med Biol 2016; 930: 25-49
- 43 Chekeni FB, Elliott MR, Sandilos JK. , et al. Pannexin 1 channels mediate ‘find-me’ signal release and membrane permeability during apoptosis. Nature 2010; 467 (7317): 863-867
- 44 Elliott MR, Chekeni FB, Trampont PC. , et al. Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature 2009; 461 (7261): 282-286
- 45 Truman LA, Ford CA, Pasikowska M. , et al. CX3CL1/fractalkine is released from apoptotic lymphocytes to stimulate macrophage chemotaxis. Blood 2008; 112 (13) 5026-5036
- 46 Lauber K, Bohn E, Kröber SM. , et al. Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Cell 2003; 113 (06) 717-730
- 47 Gude DR, Alvarez SE, Paugh SW. , et al. Apoptosis induces expression of sphingosine kinase 1 to release sphingosine-1-phosphate as a “come-and-get-me” signal. FASEB J 2008; 22 (08) 2629-2638
- 48 Segawa K, Nagata S. An apoptotic ‘eat me’ signal: phosphatidylserine exposure. Trends Cell Biol 2015; 25 (11) 639-650
- 49 Gardai SJ, McPhillips KA, Frasch SC. , et al. Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte. Cell 2005; 123 (02) 321-334
- 50 Park D, Tosello-Trampont AC, Elliott MR. , et al. BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature 2007; 450 (7168): 430-434
- 51 Kobayashi N, Karisola P, Peña-Cruz V. , et al. TIM-1 and TIM-4 glycoproteins bind phosphatidylserine and mediate uptake of apoptotic cells. Immunity 2007; 27 (06) 927-940
- 52 Freeman GJ, Casasnovas JM, Umetsu DT, DeKruyff RH. TIM genes: a family of cell surface phosphatidylserine receptors that regulate innate and adaptive immunity. Immunol Rev 2010; 235 (01) 172-189
- 53 Umetsu SE, Lee WL, McIntire JJ. , et al. TIM-1 induces T cell activation and inhibits the development of peripheral tolerance. Nat Immunol 2005; 6 (05) 447-454
- 54 Anderson AC, Anderson DE, Bregoli L. , et al. Promotion of tissue inflammation by the immune receptor Tim-3 expressed on innate immune cells. Science 2007; 318 (5853): 1141-1143
- 55 Scott CL, Zheng F, De Baetselier P. , et al. Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells. Nat Commun 2016; 7: 10321
- 56 Devisscher L, Scott CL, Lefere S. , et al. Non-alcoholic steatohepatitis induces transient changes within the liver macrophage pool. Cell Immunol 2017; 322: 74-83
- 57 Martinez J, Almendinger J, Oberst A. , et al. Microtubule-associated protein 1 light chain 3 alpha (LC3)-associated phagocytosis is required for the efficient clearance of dead cells. Proc Natl Acad Sci U S A 2011; 108 (42) 17396-17401
- 58 Baghdadi M, Nagao H, Yoshiyama H. , et al. Combined blockade of TIM-3 and TIM-4 augments cancer vaccine efficacy against established melanomas. Cancer Immunol Immunother 2013; 62 (04) 629-637
- 59 Cheng L, Ruan Z. Tim-3 and Tim-4 as the potential targets for antitumor therapy. Hum Vaccin Immunother 2015; 11 (10) 2458-2462
- 60 Du W, Yang M, Turner A. , et al. TIM-3 as a target for cancer immunotherapy and mechanisms of action. Int J Mol Sci 2017; 18 (03) 18
- 61 Nishi C, Toda S, Segawa K, Nagata S. Tim4- and MerTK-mediated engulfment of apoptotic cells by mouse resident peritoneal macrophages. Mol Cell Biol 2014; 34 (08) 1512-1520
- 62 Rantakari P, Patten DA, Valtonen J. , et al. Stabilin-1 expression defines a subset of macrophages that mediate tissue homeostasis and prevent fibrosis in chronic liver injury. Proc Natl Acad Sci U S A 2016; 113 (33) 9298-9303
- 63 Park SY, Jung MY, Kim HJ. , et al. Rapid cell corpse clearance by stabilin-2, a membrane phosphatidylserine receptor. Cell Death Differ 2008; 15 (01) 192-201
- 64 Borrego F. The CD300 molecules: an emerging family of regulators of the immune system. Blood 2013; 121 (11) 1951-1960
- 65 Voss OH, Tian L, Murakami Y, Coligan JE, Krzewski K. Emerging role of CD300 receptors in regulating myeloid cell efferocytosis. Mol Cell Oncol 2015; 2 (04) e964625
- 66 Rothlin CV, Carrera-Silva EA, Bosurgi L, Ghosh S. TAM receptor signaling in immune homeostasis. Annu Rev Immunol 2015; 33: 355-391
- 67 Mukherjee SK, Wilhelm A, Antoniades CG. TAM receptor tyrosine kinase function and the immunopathology of liver disease. Am J Physiol Gastrointest Liver Physiol 2016; 310 (11) G899-G905
- 68 Petta S, Valenti L, Marra F. , et al. MERTK rs4374383 polymorphism affects the severity of fibrosis in non-alcoholic fatty liver disease. J Hepatol 2016; 64 (03) 682-690
- 69 Janko C, Franz S, Munoz LE. , et al. CRP/anti-CRP antibodies assembly on the surfaces of cell remnants switches their phagocytic clearance toward inflammation. Front Immunol 2011; 2: 70
- 70 Elliott MR, Ravichandran KS. Clearance of apoptotic cells: implications in health and disease. J Cell Biol 2010; 189 (07) 1059-1070
- 71 Szondy Z, Garabuczi E, Joós G, Tsay GJ, Sarang Z. Impaired clearance of apoptotic cells in chronic inflammatory diseases: therapeutic implications. Front Immunol 2014; 5: 354
- 72 Chen W, Frank ME, Jin W, Wahl SM. TGF-beta released by apoptotic T cells contributes to an immunosuppressive milieu. Immunity 2001; 14 (06) 715-725
- 73 Gao Y, Herndon JM, Zhang H, Griffith TS, Ferguson TA. Anti-inflammatory effects of CD95 ligand (FasL)-induced apoptosis. J Exp Med 1998; 188 (05) 887-896
- 74 Levings MK, Bacchetta R, Schulz U, Roncarolo MG. The role of IL-10 and TGF-beta in the differentiation and effector function of T regulatory cells. Int Arch Allergy Immunol 2002; 129 (04) 263-276
- 75 Sen P, Wallet MA, Yi Z. , et al. Apoptotic cells induce Mer tyrosine kinase–dependent blockade of NF-kappaB activation in dendritic cells. Blood 2007; 109 (02) 653-660
- 76 Yoon YS, Kim SY, Kim MJ, Lim JH, Cho MS, Kang JL. PPARγ activation following apoptotic cell instillation promotes resolution of lung inflammation and fibrosis via regulation of efferocytosis and proresolving cytokines. Mucosal Immunol 2015; 8 (05) 1031-1046
- 77 Garabuczi É, Sarang Z, Szondy Z. Glucocorticoids enhance prolonged clearance of apoptotic cells by upregulating liver X receptor, peroxisome proliferator-activated receptor-δ and UCP2. Biochim Biophys Acta 2015; 1853 (03) 573-582
- 78 Li Z, Zhao J, Zhang S, Weinman SA. FOXO3-dependent apoptosis limits alcohol-induced liver inflammation by promoting infiltrating macrophage differentiation. Cell Death Dis 2018; 4: 16
- 79 Saha B, Bala S, Hosseini N, Kodys K, Szabo G. Krüppel-like factor 4 is a transcriptional regulator of M1/M2 macrophage polarization in alcoholic liver disease. J Leukoc Biol 2015; 97 (05) 963-973
- 80 Tikhanovich I, Zhao J, Olson J. , et al. Protein arginine methyltransferase 1 modulates innate immune responses through regulation of peroxisome proliferator-activated receptor γ-dependent macrophage differentiation. J Biol Chem 2017; 292 (17) 6882-6894
- 81 Odegaard JI, Ricardo-Gonzalez RR, Goforth MH. , et al. Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance. Nature 2007; 447 (7148): 1116-1120
- 82 Odegaard JI, Ricardo-Gonzalez RR, Red Eagle A. , et al. Alternative M2 activation of Kupffer cells by PPARdelta ameliorates obesity-induced insulin resistance. Cell Metab 2008; 7 (06) 496-507
- 83 Pello OM. Macrophages and c-Myc cross paths. OncoImmunology 2016; 5 (06) e1151991
- 84 Pello OM, De Pizzol M, Mirolo M. , et al. Role of c-MYC in alternative activation of human macrophages and tumor-associated macrophage biology. Blood 2012; 119 (02) 411-421
- 85 Chistiakov DA, Myasoedova VA, Revin VV, Orekhov AN, Bobryshev YV. The impact of interferon-regulatory factors to macrophage differentiation and polarization into M1 and M2. Immunobiology 2018; 223 (01) 101-111
- 86 Moshkovits I, Karo-Atar D, Itan M. , et al. CD300f associates with IL-4 receptor α and amplifies IL-4-induced immune cell responses. Proc Natl Acad Sci U S A 2015; 112 (28) 8708-8713
- 87 Miao EA, Leaf IA, Treuting PM. , et al. Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria. Nat Immunol 2010; 11 (12) 1136-1142
- 88 Cervantes J, Nagata T, Uchijima M, Shibata K, Koide Y. Intracytosolic Listeria monocytogenes induces cell death through caspase-1 activation in murine macrophages. Cell Microbiol 2008; 10 (01) 41-52
- 89 Sun GW, Lu J, Pervaiz S, Cao WP, Gan YH. Caspase-1 dependent macrophage death induced by Burkholderia pseudomallei. Cell Microbiol 2005; 7 (10) 1447-1458
- 90 Lawlor KE, Khan N, Mildenhall A. , et al. RIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL. Nat Commun 2015; 6: 6282
- 91 Knodler LA, Crowley SM, Sham HP. , et al. Noncanonical inflammasome activation of caspase-4/caspase-11 mediates epithelial defenses against enteric bacterial pathogens. Cell Host Microbe 2014; 16 (02) 249-256
- 92 Casson CN, Copenhaver AM, Zwack EE. , et al. Caspase-11 activation in response to bacterial secretion systems that access the host cytosol. PLoS Pathog 2013; 9 (06) e1003400
- 93 Senerovic L, Tsunoda SP, Goosmann C. , et al. Spontaneous formation of IpaB ion channels in host cell membranes reveals how Shigella induces pyroptosis in macrophages. Cell Death Dis 2012; 3: e384
- 94 Shi J, Zhao Y, Wang Y. , et al. Inflammatory caspases are innate immune receptors for intracellular LPS. Nature 2014; 514 (7521): 187-192
- 95 Behar SM, Martin CJ, Booty MG. , et al. Apoptosis is an innate defense function of macrophages against Mycobacterium tuberculosis. Mucosal Immunol 2011; 4 (03) 279-287
- 96 Blériot C, Dupuis T, Jouvion G, Eberl G, Disson O, Lecuit M. Liver-resident macrophage necroptosis orchestrates type 1 microbicidal inflammation and type-2-mediated tissue repair during bacterial infection. Immunity 2015; 42 (01) 145-158
- 97 Xaus J, Comalada M, Valledor AF. , et al. LPS induces apoptosis in macrophages mostly through the autocrine production of TNF-alpha. Blood 2000; 95 (12) 3823-3831
- 98 Uchikura K, Wada T, Hoshino S. , et al. Lipopolysaccharides induced increases in Fas ligand expression by Kupffer cells via mechanisms dependent on reactive oxygen species. Am J Physiol Gastrointest Liver Physiol 2004; 287 (03) G620-G626
- 99 Takei Y, Kawano S, Nishimura Y. , et al. Apoptosis: a new mechanism of endothelial and Kupffer cell killing. J Gastroenterol Hepatol 1995; 10 (Suppl. 01) S65-S67
- 100 Sladek Z, Rysanek D. Apoptosis of resident and inflammatory macrophages before and during the inflammatory response of the virgin bovine mammary gland. Acta Vet Scand 2010; 52: 12
- 101 Singhal PC, Reddy K, Ding G. , et al. Ethanol-induced macrophage apoptosis: the role of TGF-beta. J Immunol 1999; 162 (05) 3031-3036
- 102 Schilling JD, Machkovech HM, He L, Diwan A, Schaffer JE. TLR4 activation under lipotoxic conditions leads to synergistic macrophage cell death through a TRIF-dependent pathway. J Immunol 2013; 190 (03) 1285-1296
- 103 Navarre WW, Zychlinsky A. Pathogen-induced apoptosis of macrophages: a common end for different pathogenic strategies. Cell Microbiol 2000; 2 (04) 265-273
- 104 Mangan DF, Robertson B, Wahl SM. IL-4 enhances programmed cell death (apoptosis) in stimulated human monocytes. J Immunol 1992; 148 (06) 1812-1816
- 105 Liu C, Tao Q, Sun M. , et al. Kupffer cells are associated with apoptosis, inflammation and fibrotic effects in hepatic fibrosis in rats. Lab Invest 2010; 90 (12) 1805-1816
- 106 Li B, Zhang H, Zeng M. , et al. Bone marrow mesenchymal stem cells protect alveolar macrophages from lipopolysaccharide-induced apoptosis partially by inhibiting the Wnt/β-catenin pathway. Cell Biol Int 2015; 39 (02) 192-200
- 107 Lee EJ, Lee YR, Joo HK. , et al. Arginase II inhibited lipopolysaccharide-induced cell death by regulation of iNOS and Bcl-2 family proteins in macrophages. Mol Cells 2013; 35 (05) 396-401
- 108 Kim YC, Song SB, Lee SK, Park SM, Kim YS. The nuclear orphan receptor NR4A1 is involved in the apoptotic pathway induced by LPS and Simvastatin in RAW 264.7 macrophages. Immune Netw 2014; 14 (02) 116-122
- 109 Kearns MT, Barthel L, Bednarek JM, Yunt ZX, Henson PM, Janssen WJ. Fas ligand-expressing lymphocytes enhance alveolar macrophage apoptosis in the resolution of acute pulmonary inflammation. Am J Physiol Lung Cell Mol Physiol 2014; 307 (01) L62-L70
- 110 Cuesta N, Nhu QM, Zudaire E, Polumuri S, Cuttitta F, Vogel SN. IFN regulatory factor-2 regulates macrophage apoptosis through a STAT1/3- and caspase-1-dependent mechanism. J Immunol 2007; 178 (06) 3602-3611
- 111 Chen S, Yuan J, Yao S. , et al. Lipopolysaccharides may aggravate apoptosis through accumulation of autophagosomes in alveolar macrophages of human silicosis. Autophagy 2015; 11 (12) 2346-2357
- 112 Bingisser R, Stey C, Weller M, Groscurth P, Russi E, Frei K. Apoptosis in human alveolar macrophages is induced by endotoxin and is modulated by cytokines. Am J Respir Cell Mol Biol 1996; 15 (01) 64-70
- 113 Li Z, Scott MJ, Fan EK. , et al. Tissue damage negatively regulates LPS-induced macrophage necroptosis. Cell Death Differ 2016; 23 (09) 1428-1447
- 114 He S, Liang Y, Shao F, Wang X. Toll-like receptors activate programmed necrosis in macrophages through a receptor-interacting kinase-3-mediated pathway. Proc Natl Acad Sci U S A 2011; 108 (50) 20054-20059
- 115 Li Z, Zhao J, Tikhanovich I. , et al. Serine 574 phosphorylation alters transcriptional programming of FOXO3 by selectively enhancing apoptotic gene expression. Cell Death Differ 2016; 23 (04) 583-595
- 116 Thurman RG, Bradford BU, Iimuro Y. , et al. Mechanisms of alcohol-induced hepatotoxicity: studies in rats. Front Biosci 1999; 4: e42-e46
- 117 Adachi Y, Bradford BU, Gao W, Bojes HK, Thurman RG. Inactivation of Kupffer cells prevents early alcohol-induced liver injury. Hepatology 1994; 20 (02) 453-460
- 118 Lee J, French B, Morgan T, French SW. The liver is populated by a broad spectrum of markers for macrophages. In alcoholic hepatitis the macrophages are M1 and M2. Exp Mol Pathol 2014; 96 (01) 118-125
- 119 Szabo G. Gut-liver axis in alcoholic liver disease. Gastroenterology 2015; 148 (01) 30-36
- 120 Bertola A, Mathews S, Ki SH, Wang H, Gao B. Mouse model of chronic and binge ethanol feeding (the NIAAA model). Nat Protoc 2013; 8 (03) 627-637
- 121 Bertola A, Park O, Gao B. Chronic plus binge ethanol feeding synergistically induces neutrophil infiltration and liver injury in mice: a critical role for E-selectin. Hepatology 2013; 58 (05) 1814-1823
- 122 Cohen JI, Roychowdhury S, McMullen MR, Stavitsky AB, Nagy LE. Complement and alcoholic liver disease: role of C1q in the pathogenesis of ethanol-induced liver injury in mice. Gastroenterology 2010; 139 (02) 664-674 , 674.e1
- 123 Baeck C, Wehr A, Karlmark KR. , et al. Pharmacological inhibition of the chemokine CCL2 (MCP-1) diminishes liver macrophage infiltration and steatohepatitis in chronic hepatic injury. Gut 2012; 61 (03) 416-426
- 124 Miura K, Yang L, van Rooijen N, Ohnishi H, Seki E. Hepatic recruitment of macrophages promotes nonalcoholic steatohepatitis through CCR2. Am J Physiol Gastrointest Liver Physiol 2012; 302 (11) G1310-G1321
- 125 Kruger AJ, Fuchs BC, Masia R. , et al. Prolonged cenicriviroc therapy reduces hepatic fibrosis despite steatohepatitis in a diet-induced mouse model of nonalcoholic steatohepatitis. Hepatol Commun 2018; 2 (05) 529-545
- 126 Tosello-Trampont AC, Landes SG, Nguyen V, Novobrantseva TI, Hahn YS. Kuppfer cells trigger nonalcoholic steatohepatitis development in diet-induced mouse model through tumor necrosis factor-α production. J Biol Chem 2012; 287 (48) 40161-40172
- 127 Nakashima H, Nakashima M, Kinoshita M. , et al. Activation and increase of radio-sensitive CD11b+ recruited Kupffer cells/macrophages in diet-induced steatohepatitis in FGF5 deficient mice. Sci Rep 2016; 6: 34466
- 128 Itoh M, Suganami T, Kato H. , et al. CD11c+ resident macrophages drive hepatocyte death-triggered liver fibrosis in a murine model of nonalcoholic steatohepatitis. JCI Insight 2017; 2 (22) 2
- 129 Svendsen P, Graversen JH, Etzerodt A. , et al. Antibody-directed glucocorticoid targeting to CD163 in M2-type macrophages attenuates fructose-induced liver inflammatory changes. Mol Ther Methods Clin Dev 2016; 4: 50-61
- 130 Reid DT, Reyes JL, McDonald BA, Vo T, Reimer RA, Eksteen B. Kupffer cells undergo fundamental changes during the development of experimental NASH and are critical in initiating liver damage and inflammation. PLoS One 2016; 11 (07) e0159524
- 131 Holt MP, Cheng L, Ju C. Identification and characterization of infiltrating macrophages in acetaminophen-induced liver injury. J Leukoc Biol 2008; 84 (06) 1410-1421
- 132 Graubardt N, Vugman M, Mouhadeb O. , et al. Ly6Chi monocytes and their macrophage descendants regulate neutrophil function and clearance in acetaminophen-induced liver injury. Front Immunol 2017; 8: 626
- 133 Wynn TA, Vannella KM. Macrophages in tissue repair, regeneration, and fibrosis. Immunity 2016; 44 (03) 450-462
- 134 Rehermann B. Mature peritoneal macrophages take an avascular route into the injured liver and promote tissue repair. Hepatology 2017; 65 (01) 376-379
- 135 Schnabl B, Brenner DA. Interactions between the intestinal microbiome and liver diseases. Gastroenterology 2014; 146 (06) 1513-1524
- 136 Dapito DH, Mencin A, Gwak GY. , et al. Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4. Cancer Cell 2012; 21 (04) 504-516
- 137 Mazagova M, Wang L, Anfora AT. , et al. Commensal microbiota is hepatoprotective and prevents liver fibrosis in mice. FASEB J 2015; 29 (03) 1043-1055
- 138 Baeck C, Wei X, Bartneck M. , et al. Pharmacological inhibition of the chemokine C-C motif chemokine ligand 2 (monocyte chemoattractant protein 1) accelerates liver fibrosis regression by suppressing Ly-6C(+) macrophage infiltration in mice. Hepatology 2014; 59 (03) 1060-1072
- 139 Bartneck M, Warzecha KT, Tacke F. Therapeutic targeting of liver inflammation and fibrosis by nanomedicine. Hepatobiliary Surg Nutr 2014; 3 (06) 364-376
- 140 Bartneck M, Scheyda KM, Warzecha KT. , et al. Fluorescent cell-traceable dexamethasone-loaded liposomes for the treatment of inflammatory liver diseases. Biomaterials 2015; 37: 367-382
- 141 He C, Yin L, Tang C, Yin C. Multifunctional polymeric nanoparticles for oral delivery of TNF-α siRNA to macrophages. Biomaterials 2013; 34 (11) 2843-2854
- 142 Thomas JA, Pope C, Wojtacha D. , et al. Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function. Hepatology 2011; 53 (06) 2003-2015
- 143 Traber PG, Chou H, Zomer E. , et al. Regression of fibrosis and reversal of cirrhosis in rats by galectin inhibitors in thioacetamide-induced liver disease. PLoS One 2013; 8 (10) e75361
- 144 Szondy Z, Sarang Z, Kiss B, Garabuczi É, Köröskényi K. Anti-inflammatory mechanisms triggered by apoptotic cells during their clearance. Front Immunol 2017; 8: 909
- 145 Wallach D, Kang TB, Kovalenko A. Concepts of tissue injury and cell death in inflammation: a historical perspective. Nat Rev Immunol 2014; 14 (01) 51-59
- 146 Saas P, Bonnefoy F, Toussirot E, Perruche S. Harnessing apoptotic cell clearance to treat autoimmune arthritis. Front Immunol 2017; 8: 1191
- 147 Zhang M, Xu S, Han Y, Cao X. Apoptotic cells attenuate fulminant hepatitis by priming Kupffer cells to produce interleukin-10 through membrane-bound TGF-β. Hepatology 2011; 53 (01) 306-316
- 148 Wu C, Zhang Y, Jiang Y. , et al. Apoptotic cell administration enhances pancreatic islet engraftment by induction of regulatory T cells and tolerogenic dendritic cells. Cell Mol Immunol 2013; 10 (05) 393-402
- 149 Wang Z, Shufesky WJ, Montecalvo A, Divito SJ, Larregina AT, Morelli AE. In situ-targeting of dendritic cells with donor-derived apoptotic cells restrains indirect allorecognition and ameliorates allograft vasculopathy. PLoS One 2009; 4 (03) e4940
- 150 Wang Z, Larregina AT, Shufesky WJ. , et al. Use of the inhibitory effect of apoptotic cells on dendritic cells for graft survival via T-cell deletion and regulatory T cells. Am J Transplant 2006; 6 (06) 1297-1311
- 151 Sun E, Gao Y, Chen J. , et al. Allograft tolerance induced by donor apoptotic lymphocytes requires phagocytosis in the recipient. Cell Death Differ 2004; 11 (12) 1258-1264
- 152 Perruche S, Kleinclauss F, Bittencourt MdeC, Paris D, Tiberghien P, Saas P. Intravenous infusion of apoptotic cells simultaneously with allogeneic hematopoietic grafts alters anti-donor humoral immune responses. Am J Transplant 2004; 4 (08) 1361-1365
- 153 Tacke F, Trautwein C. Mechanisms of liver fibrosis resolution. J Hepatol 2015; 63 (04) 1038-1039
- 154 Mevorach D, Zuckerman T, Reiner I. , et al. Single infusion of donor mononuclear early apoptotic cells as prophylaxis for graft-versus-host disease in myeloablative HLA-matched allogeneic bone marrow transplantation: a phase I/IIa clinical trial. Biol Blood Marrow Transplant 2014; 20 (01) 58-65
- 155 King A, Barton D, Beard HA. , et al. REpeated AutoLogous Infusions of STem cells In Cirrhosis (REALISTIC): a multicentre, phase II, open-label, randomised controlled trial of repeated autologous infusions of granulocyte colony-stimulating factor (GCSF) mobilised CD133+ bone marrow stem cells in patients with cirrhosis. A study protocol for a randomised controlled trial. BMJ Open 2015; 5 (03) e007700