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Mechanisms of continual efferocytosis by macrophages and its role in mitigating atherosclerosis

Mechanisms of continual efferocytosis by macrophages and its role in mitigating atherosclerosis

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DOI	10.1097/IN9.0000000000000017
刊名	Immunometabolism IJ
年，卷(期)	2023, 5(1)
作者	Kumar, Dhananjay; Pandit, Rajan; Yurdagul Jr, Arif,
作者单位	[Kumar, Dhananjay; Pandit, Rajan; Yurdagul Jr, Arif] Louisiana State Univ, Hlth Sci Ctr Shreveport, Mol & Cellular Physiol, Shreveport, LA 71115 USA
摘要	Atherosclerotic cardiovascular disease is the leading cause of death worldwide. Rupture-prone atheromas that give rise to myocardial infarction and stroke are characterized by the presence of a necrotic core and a thin fibrous cap. During homeostasis, cellular debris and apoptotic cells are cleared quickly through a process termed efferocytosis. However, clearance of apoptotic cells is significantly compromised in many chronic inflammatory diseases, including atherosclerosis. Emerging evidence suggests that impairments in efferocytosis drive necrotic core formation and contribute significantly to plaque vulnerability. Recently, it has been appreciated that successive rounds of efferocytosis, termed continual efferocytosis, is mechanistically distinct from single efferocytosis and relies heavily on the metabolism and handling of apoptotic cell-derived cargo. In vivo, selective defects in continual efferocytosis drive secondary necrosis, impair inflammation resolution, and worsen atherosclerosis. This Mini Review focuses on our current understanding of the cellular and molecular mechanisms of continual efferocytosis and how dysregulations in this process mediate nonresolving inflammation. We will also discuss possible strategies to enhance efferocytosis when it fails.
Abstract	Atherosclerotic cardiovascular disease is the leading cause of death worldwide. Rupture-prone atheromas that give rise to myocardial infarction and stroke are characterized by the presence of a necrotic core and a thin fibrous cap. During homeostasis, cellular debris and apoptotic cells are cleared quickly through a process termed efferocytosis. However, clearance of apoptotic cells is significantly compromised in many chronic inflammatory diseases, including atherosclerosis. Emerging evidence suggests that impairments in efferocytosis drive necrotic core formation and contribute significantly to plaque vulnerability. Recently, it has been appreciated that successive rounds of efferocytosis, termed continual efferocytosis, is mechanistically distinct from single efferocytosis and relies heavily on the metabolism and handling of apoptotic cell-derived cargo. In vivo, selective defects in continual efferocytosis drive secondary necrosis, impair inflammation resolution, and worsen atherosclerosis. This Mini Review focuses on our current understanding of the cellular and molecular mechanisms of continual efferocytosis and how dysregulations in this process mediate nonresolving inflammation. We will also discuss possible strategies to enhance efferocytosis when it fails.
关键词	efferocytosis; macrophages; atherosclerosis
KeyWord	efferocytosis; macrophages; atherosclerosis
基金项目
页码	1-5

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[1]. Libby P, Buring JE, Badimon L, et al. Atherosclerosis. Nat Rev Dis Primers. 2019;5(1):56. doi: 10.1038/s41572-019-0106-z.

[2]. Yurdagul A Jr, Finney AC, Woolard MD, et al. The arterial microenvironment: the where and why of atherosclerosis. Biochem J. 2016;473(10):1281–95. doi: 10.1042/BJ20150844.

[3]. Yurdagul A Jr, Orr AW. Blood brothers: hemodynamics and cell-matrix interactions in endothelial function. Antioxid Redox Signal. 2016;25(7):415–34. doi: 10.1089/ars.2015.6525.

[4]. Tabas I, Garcia-Cardena G, Owens GK. Recent insights into the cellular biology of atherosclerosis. J Cell Biol. 2015;209(1):13–22. doi: 10.1083/jcb.201412052.

[5]. Wintergerst ES, Jelk J, Rahner C, et al. Apoptosis induced by oxidized low density lipoprotein in human monocyte-derived macrophages involves CD36 and activation of caspase-3. Eur J Biochem. 2000;267(19):6050–9. doi: 10.1046/j.1432-1327.2000.01682.x.

[6]. Yin C, Heit B. Cellular responses to the efferocytosis of apoptotic cells. Front Immunol. 2021;12:631714. doi: 10.3389/fimmu.2021.631714.

[7]. Henson PM, Bratton DL, Fadok VA. Apoptotic cell removal. Curr Biol. 2001;11(19):R795–805. doi: 10.1016/s0960-9822(01)00474-2.

[8]. Doran AC, Yurdagul A Jr, Tabas I. Efferocytosis in health and disease. Nat Rev Immunol. 2020;20(4):254–67. doi: 10.1038/s41577-019-0240-6.

[9]. Yurdagul A Jr. Metabolic consequences of efferocytosis and its impact on atherosclerosis. Immunometabolism. 2021;3(2):e210017. doi: 10.20900/immunometab20210017.

[10]. Yurdagul A Jr, Doran AC, Cai B, et al. Mechanisms and consequences of defective efferocytosis in atherosclerosis. Front Cardiovasc Med. 2017;4:86. doi: 10.3389/fcvm.2017.00086.

[11]. Orecchioni M, Ghosheh Y, Pramod AB, et al. Macrophage polarization: different gene signatures in M1(LPS+) vs. classically and M2(LPS-) vs. alternatively activated macrophages. Front Immunol. 2019;10:1084. doi: 10.3389/fimmu.2019.01084.

[12]. Murray PJ. Macrophage polarization. Annu Rev Physiol. 2017;79:541–66. doi: 10.1146/annurev-physiol-022516-034339.

[13]. Lawrence T, Natoli G. Transcriptional regulation of macrophage polarization: enabling diversity with identity. Nat Rev Immunol. 2011;11(11):750–61. doi: 10.1038/nri3088.

[14]. Mohd Idrus FN, Ahmad NS, Hoe CH, et al. Differential polarization and the expression of efferocytosis receptor MerTK on M1 and M2 macrophages isolated from coronary artery disease patients. BMC Immunol. 2021;22(1):21. doi: 10.1186/s12865-021-00410-2.

[15]. Sakhno LV, Shevela EY, Tikhonova MA, et al. Efferocytosis modulates Arginase-1 and tyrosine kinase Mer expression in GM-CSF-differentiated human macrophages. Bull Exp Biol Med. 2021;170(6):778–81. doi: 10.1007/s10517-021-05153-z.

[16]. Morioka S, Maueroder C, Ravichandran KS. Living on the edge: efferocytosis at the interface of homeostasis and pathology. Immunity. 2019;50(5):1149–62. doi: 10.1016/j.immuni.2019.04.018.

[17]. Poon IK, Lucas CD, Rossi AG, et al. Apoptotic cell clearance: basic biology and therapeutic potential. Nat Rev Immunol. 2014;14(3):166–80. doi: 10.1038/nri3607.

[18]. Truman LA, Ford CA, Pasikowska M, et al. CX3CL1/fractalkine is released from apoptotic lymphocytes to stimulate macrophage chemotaxis. Blood. 2008;112(13):5026–36. doi: 10.1182/blood-2008-06-162404.

[19]. 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(8):2629–38. doi: 10.1096/fj.08-107169.

[20]. Lauber K, Bohn E, Krober SM, et al. Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Cell. 2003;113(6):717–30. doi: 10.1016/s0092-8674(03)00422-7.

[21]. Mueller RB, Sheriff A, Gaipl US, et al. Attraction of phagocytes by apoptotic cells is mediated by lysophosphatidylcholine. Autoimmunity. 2007;40(4):342–4. doi: 10.1080/08916930701356911.

[22]. 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):282–6. doi: 10.1038/nature08296.

[23]. Yamaguchi H, Maruyama T, Urade Y, et al. Immunosuppression via adenosine receptor activation by adenosine monophosphate released from apoptotic cells. Elife. 2014;3:e02172. doi: 10.7554/eLife.02172.

[24]. Park SY, Jung MY, Kim HJ, et al. Rapid cell corpse clearance by stabilin-2, a membrane phosphatidylserine receptor. Cell Death Differ. 2008;15(1):192–201. doi: 10.1038/sj.cdd.4402242.

[25]. Kim D, Lee SA, Moon H, et al. The Tim gene family in efferocytosis. Genes Genomics. 2020;42(9):979–86. doi: 10.1007/s13258-020-00969-x.

[26]. Scott RS, McMahon EJ, Pop SM, et al. Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature. 2001;411(6834):207–11. doi: 10.1038/35075603.

[27]. Cai B, Kasikara C, Doran AC, et al. MerTK signaling in macrophages promotes the synthesis of inflammation resolution mediators by suppressing CaMKII activity. Sci Signal. 2018;11(549):eaar3721. doi: 10.1126/scisignal.aar3721.

[28]. Vago JP, Amaral FA, van de Loo FAJ. Resolving inflammation by TAM receptor activation. Pharmacol Ther. 2021;227:107893. doi: 10.1016/j.pharmthera.2021.107893.

[29]. Zizzo G, Hilliard BA, Monestier M, et al. Efficient clearance of early apoptotic cells by human macrophages requires M2c polarization and MerTK induction. J Immunol. 2012;189(7):3508–20. doi: 10.4049/jimmunol.1200662.

[30]. Sanjuan MA, Dillon CP, Tait SW, et al. Toll-like receptor signalling in macrophages links the autophagy pathway to phagocytosis. Nature. 2007;450(7173):1253–7. doi: 10.1038/nature06421.

[31]. Martinez J, Malireddi RK, Lu Q, et al. Molecular characterization of LC3-associated phagocytosis reveals distinct roles for Rubicon, NOX2 and autophagy proteins. Nat Cell Biol. 2015;17(7):893–906. doi: 10.1038/ncb3192.

[32]. Yurdagul A Jr, Subramanian M, Wang X, et al. Macrophage metabolism of apoptotic cell-derived arginine promotes continual efferocytosis and resolution of injury. Cell Metab. 2020;31(3):518–33.e10. doi: 10.1016/j.cmet.2020.01.001.

[33]. Mao Y, Finnemann SC. Regulation of phagocytosis by Rho GTPases. Small GTPases. 2015;6(2):89–99. doi: 10.4161/21541248.2014.989785.

[34]. Yurdagul A Jr, Kong N, Gerlach BD, et al. ODC (ornithine decarboxylase)-dependent putrescine synthesis maintains MerTK (MER Tyrosine-Protein Kinase) expression to drive resolution. Arterioscler Thromb Vasc Biol. 2021;41(3):e144–59. doi: 10.1161/ATVBAHA.120.315622.

[35]. Ampomah PB, Cai B, Sukka SR, et al. Macrophages use apoptotic cell-derived methionine and DNMT3A during efferocytosis to promote tissue resolution. Nat Metab. 2022;4(4):444–57. doi: 10.1038/s42255-022-00551-7.

[36]. Yvan-Charvet L, Pagler TA, Seimon TA, et al. ABCA1 and ABCG1 protect against oxidative stress-induced macrophage apoptosis during efferocytosis. Circ Res. 2010;106(12):1861–9. doi: 10.1161/CIRCRESAHA.110.217281.

[37]. Viaud M, Ivanov S, Vujic N, et al. Lysosomal cholesterol hydrolysis couples efferocytosis to anti-inflammatory oxysterol production. Circ Res. 2018;122(10):1369–84. doi: 10.1161/CIRCRESAHA.117.312333.

[38]. Isfort K, Ebert F, Bornhorst J, et al. Real-time imaging reveals that P2Y2 and P2Y12 receptor agonists are not chemoattractants and macrophage chemotaxis to complement C5a is phosphatidylinositol 3-kinase (PI3K)- and p38 mitogen-activated protein kinase (MAPK)-independent. J Biol Chem. 2011;286(52):44776–87. doi: 10.1074/jbc.M111.289793.

[39]. Gerlach BD, Ampomah PB, Yurdagul A Jr, et al. Efferocytosis induces macrophage proliferation to help resolve tissue injury. Cell Metab. 2021;33(12):2445–63.e8. doi: 10.1016/j.cmet.2021.10.015.

[40]. Morioka S, Perry JSA, Raymond MH, et al. Efferocytosis induces a novel SLC program to promote glucose uptake and lactate release. Nature. 2018;563(7733):714–8. doi: 10.1038/s41586-018-0735-5. E.

[41]. Zhang S, Weinberg S, DeBerge M, et al. Efferocytosis fuels requirements of fatty acid oxidation and the electron transport chain to polarize macrophages for tissue repair. Cell Metab. 2019;29(2):443–56.e5. doi: 10.1016/j.cmet.2018.12.004.

[42]. Wang Y-T, Trzeciak AJ, Rojas WS, et al. Cell Metab. 2022;S1550-4131(22)00542-3. doi: 10.1016/j.cmet.2022.12.005.

[43]. Park D, Han CZ, Elliott MR, et al. Continued clearance of apoptotic cells critically depends on the phagocyte Ucp2 protein. Nature. 2011;477(7363):220–4. doi: 10.1038/nature10340.

[44]. Wang Y, Subramanian M, Yurdagul A Jr, et al. Mitochondrial fission promotes the continued clearance of apoptotic cells by macrophages. Cell. 2017;171(2):331–45.e22. doi: 10.1016/j.cell.2017.08.041.

[45]. Pan L, Bai P, Weng X, et al. Legumain is an endogenous modulator of integrin alphavbeta3 triggering vascular degeneration, dissection, and rupture. Circulation. 2022;145(9):659–74. doi: 10.1161/CIRCULATIONAHA.121.056640.

[46]. Yan X, He M, Huang H, et al. Endogenous H2S targets mitochondria to promote continual phagocytosis of erythrocytes by microglia after intracerebral hemorrhage. Redox Biol. 2022;56:102442. doi: 10.1016/j.redox.2022.102442.

[47]. Low Wang CC, Hess CN, Hiatt WR, et al. Clinical update: cardiovascular disease in diabetes mellitus: atherosclerotic cardiovascular disease and heart failure in type 2 diabetes mellitus - mechanisms, management, and clinical considerations. Circulation. 2016;133(24):2459–502. doi: 10.1161/CIRCULATIONAHA.116.022194.

[48]. Back M, Yurdagul A Jr, Tabas I, et al. Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities. Nat Rev Cardiol. 2019;16(7):389–406. doi: 10.1038/s41569-019-0169-2.

[49]. Tao W, Yurdagul A Jr, Kong N, et al. siRNA nanoparticles targeting CaMKIIgamma in lesional macrophages improve atherosclerotic plaque stability in mice. Sci Transl Med. 2020;12(553):eaay1063. doi: 10.1126/scitranslmed.aay1063.

[50]. Kojima Y, Volkmer JP, McKenna K, et al. CD47-blocking antibodies restore phagocytosis and prevent atherosclerosis. Nature. 2016;536(7614):86–90. doi: 10.1038/nature18935.

[51]. Singla B, Lin HP, Ahn W, et al. Loss of myeloid cell-specific SIRPalpha, but not CD47, attenuates inflammation and suppresses atherosclerosis. Cardiovasc Res. 2022;118(15):3097–111. doi: 10.1093/cvr/cvab369.

[52]. Flores AM, Hosseini-Nassab N, Jarr KU, et al. Pro-efferocytic nanoparticles are specifically taken up by lesional macrophages and prevent atherosclerosis. Nat Nanotechnol. 2020;15(2):154–61. doi: 10.1038/s41565-019-0619-3.

[53]. Chen W, Schilperoort M, Cao Y, et al. Macrophage-targeted nanomedicine for the diagnosis and treatment of atherosclerosis. Nat Rev Cardiol. 2022;19(4):228–49. doi: 10.1038/s41569-021-00629-x.

[54]. Ouimet M, Ediriweera H, Afonso MS, et al. microRNA-33 regulates macrophage autophagy in atherosclerosis. Arterioscler Thromb Vasc Biol. 2017;37(6):1058–67. doi: 10.1161/ATVBAHA.116.308916.

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Kumar, Dhananjay; Pandit, Rajan; Yurdagul Jr, Arif. Mechanisms of continual efferocytosis by macrophages and its role in mitigating atherosclerosis [J]. Immunometabolism. 2023; 5; (1). 1 - 5.

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