Advertisement

Inflammation

pp 1–14 | Cite as

Review: the Role and Mechanisms of Macrophage Autophagy in Sepsis

  • Peng Qiu
  • Yang Liu
  • Jin Zhang
REVIEW

Abstract

Sepsis is a systemic inflammatory response syndrome caused by infection. The core mechanism underlying sepsis is immune dysfunction, with macrophages, as important cells of the innate immune system, playing an essential role. Autophagy has been shown to be closely related to inflammation and immunity, and autophagy enhancement in sepsis can play a protective role by negatively regulating abnormal macrophage activation, modulating macrophage polarization phenotype, reducing activation of the inflammasome and release of inflammatory factors, and affecting macrophage apoptosis. However, excessive autophagy may also lead to autophagic death of macrophages, which further aggravates the inflammatory response. The mechanisms underlying these functions are relatively complex and remain unclear, but may be related to a variety of signaling pathways such as NF-κB, mTOR, and PI3K/AKT. The administration of drugs to assist in the regulation of macrophage autophagy has become a novel treatment for sepsis. The present review focuses on the role and the potential mechanisms of macrophage autophagy in sepsis.

KEY WORDS

macrophage autophagy sepsis inflammation immunity apoptosis polarization 

Notes

Funding Information

This work was supported by Shenyang Municipal Science and Technology Commission (Liaoning, China); Project Number 17-230-9-45.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Singer, M., C.S. Deutschman, C.W. Seymour, M. Shankar-Hari, D. Annane, M. Bauer, R. Bellomo, G.R. Bernard, J.D. Chiche, C.M. Coopersmith, R.S. Hotchkiss, M.M. Levy, J.C. Marshall, G.S. Martin, S.M. Opal, G.D. Rubenfeld, T. van der Poll, J.L. Vincent, and D.C. Angus. 2016. The Third International Consensus Definitions for sepsis and Septic Shock (Sepsis-3). JAMA 315 (8): 801–810.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Delano, M.J., and P.A. Ward. 2016. The immune system’s role in sepsis progression, resolution, and long-term outcome. Immunological Reviews 274 (1): 330–353.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Kovach, M.A., and T.J. Standiford. 2012. The function of neutrophils in sepsis. Current Opinion in Infectious Diseases 25 (3): 321–327.PubMedCrossRefGoogle Scholar
  4. 4.
    Pastille, E., et al. 2010. Modulation of dendritic cell differentiation in the bone marrow mediates sustained immunosuppression after polymicrobial sepsis. Journal of Immunology 186 (2): 977–986.CrossRefGoogle Scholar
  5. 5.
    Rimmele, T., et al. 2016. Immune cell phenotype and function in sepsis. Shock 45 (3): 282–291.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Luan, Y.-Y., N. Dong, M. Xie, X.Z. Xiao, and Y.M. Yao. 2014. The significance and regulatory mechanisms of innate immune cells in the development of sepsis. Journal of Interferon & Cytokine Research 34 (1): 2–15.CrossRefGoogle Scholar
  7. 7.
    Giamarellos-Bourboulis, E.J. 2014. Natural killer cells in sepsis: Detrimental role for final outcome. Critical Care Medicine 42 (6): 1579–1580.PubMedCrossRefGoogle Scholar
  8. 8.
    Epelman, S., K.J. Lavine, and G.J. Randolph. 2014. Origin and functions of tissue macrophages. Immunity 41 (1): 21–35.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Gordon, S., and A. Pluddemann. 2017. Tissue macrophages: heterogeneity and functions. BMC Biology 15 (1): 53.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Lauvau, G., P.’. Loke, and T.M. Hohl. 2015. Monocyte-mediated defense against bacteria, fungi, and parasites. Seminars in Immunology 27 (6): 397–409.PubMedCrossRefGoogle Scholar
  11. 11.
    Hamidzadeh, K., S.M. Christensen, E. Dalby, P. Chandrasekaran, and D.M. Mosser. 2017. Macrophages and the recovery from acute and chronic inflammation. Annual Review of Physiology 79: 567–592.PubMedCrossRefGoogle Scholar
  12. 12.
    Winkler, M.S., A. Rissiek, M. Priefler, E. Schwedhelm, L. Robbe, A. Bauer, C. Zahrte, C. Zoellner, S. Kluge, and A. Nierhaus. 2017. Human leucocyte antigen (HLA-DR) gene expression is reduced in sepsis and correlates with impaired TNFalpha response: a diagnostic tool for immunosuppression? PLoS One 12 (8): e0182427.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Wang, T.S., and J.C. Deng. 2008. Molecular and cellular aspects of sepsis-induced immunosuppression. Journal of Molecular Medicine 86 (5): 495–506.PubMedCrossRefGoogle Scholar
  14. 14.
    Lee, C.R., and D.C. Zeldin. 2015. Resolvin infectious inflammation by targeting the host response. The New England Journal of Medicine 373: 2183–2185.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Kumar, V. 2018. Targeting macrophage immunometabolism: dawn in the darkness of sepsis. International Immunopharmacology 58: 173–185.PubMedCrossRefGoogle Scholar
  16. 16.
    Levine, B., N. Mizushima, and H.W. Virgin. 2011. Autophagy in immunity and inflammation. Nature 469 (7330): 323–335.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Saitoh, T., and S. Akira. 2016. Regulation of inflammasomes by autophagy. The Journal of Allergy and Clinical Immunology 138 (1): 28–36.PubMedCrossRefGoogle Scholar
  18. 18.
    Deretic, V., T. Saitoh, and S. Akira. 2013. Autophagy in infection, inflammation and immunity. Nature Reviews Immunology 13 (10): 722–737.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Deretic, V., T. Kimura, G. Timmins, P. Moseley, S. Chauhan, and M. Mandell. 2015. Immunologic manifestations of autophagy. The Journal of Clinical Investigation 125 (1): 75–84.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Bonilla, D.L., A. Bhattacharya, Y. Sha, Y. Xu, Q. Xiang, A. Kan, C. Jagannath, M. Komatsu, and N.T. Eissa. 2013. Autophagy regulates phagocytosis by modulating the expression of scavenger receptors. Immunity 39 (3): 537–547.PubMedCrossRefGoogle Scholar
  21. 21.
    Komatsu, M., H. Kurokawa, S. Waguri, K. Taguchi, A. Kobayashi, Y. Ichimura, Y.S. Sou, I. Ueno, A. Sakamoto, K.I. Tong, M. Kim, Y. Nishito, S.I. Iemura, T. Natsume, T. Ueno, E. Kominami, H. Motohashi, K. Tanaka, and M. Yamamoto. 2010. The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nature Cell Biology 12 (3): 213–223.PubMedCrossRefGoogle Scholar
  22. 22.
    Cadwell, K., J.Y. Liu, S.L. Brown, H. Miyoshi, J. Loh, J.K. Lennerz, C. Kishi, W. Kc, J.A. Carrero, S. Hunt, C.D. Stone, E.M. Brunt, R.J. Xavier, B.P. Sleckman, E. Li, N. Mizushima, T.S. Stappenbeck, and H.W. Virgin IV. 2008. A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature 456 (7219): 259–263.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Moscat, J., and M.T. Diaz-Meco. 2009. p62 at the crossroads of autophagy, apoptosis, and cancer. Cell 137 (6): 1001–1004.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Yuk, J.M., and E.K. Jo. 2013. Crosstalk between autophagy and inflammasomes. Molecules and Cells 36 (5): 393–399.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Saitoh, T., N. Fujita, M.H. Jang, S. Uematsu, B.G. Yang, T. Satoh, H. Omori, T. Noda, N. Yamamoto, M. Komatsu, K. Tanaka, T. Kawai, T. Tsujimura, O. Takeuchi, T. Yoshimori, and S. Akira. 2008. Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Nature 456 (7219): 264–268.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Qu, X., Z. Zou, Q. Sun, K. Luby-Phelps, P. Cheng, R.N. Hogan, C. Gilpin, and B. Levine. 2007. Autophagy gene-dependent clearance of apoptotic cells during embryonic development. Cell 128 (5): 931–946.PubMedCrossRefGoogle Scholar
  27. 27.
    Chargui, A., and M.V. El May. 2014. Autophagy mediates neutrophil responses to bacterial infection. APMIS 122 (11): 1047–1058.PubMedGoogle Scholar
  28. 28.
    Schultze, J.L., and S.V. Schmidt. 2015. Molecular features of macrophage activation. Seminars in Immunology 27 (6): 416–423.PubMedCrossRefGoogle Scholar
  29. 29.
    Hotchkiss, R.S., C.M. Coopersmith, J.E. McDunn, and T.A. Ferguson. 2009. The sepsis seesaw: tilting toward immunosuppression. Nature Medicine 15 (5): 496–497.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Nakahira, K., J.A. Haspel, V.A.K. Rathinam, S.J. Lee, T. Dolinay, H.C. Lam, J.A. Englert, M. Rabinovitch, M. Cernadas, H.P. Kim, K.A. Fitzgerald, S.W. Ryter, and A.M.K. Choi. 2011. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nature Immunology 12 (3): 222–230.PubMedCrossRefGoogle Scholar
  31. 31.
    Lin, C.W., S. Lo, C. Hsu, C.H. Hsieh, Y.F. Chang, B.S. Hou, Y.H. Kao, C.C. Lin, M.L. Yu, S.S. Yuan, and Y.C. Hsieh. 2014. T-cell autophagy deficiency increases mortality and suppresses immune responses after sepsis. PLoS One 9 (7): e102066.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Mansilla Pareja, M.E., and M.I. Colombo. 2013. Autophagic clearance of bacterial pathogens: molecular recognition of intracellular microorganisms. Frontiers in Cellular and Infection Microbiology 3:54.Google Scholar
  33. 33.
    Maurer, K., T. Reyes-Robles, F. Alonzo III, J. Durbin, V.J. Torres, and K. Cadwell. 2015. Autophagy mediates tolerance to Staphylococcus aureus alpha-toxin. Cell Host & Microbe 17 (4): 429–440.CrossRefGoogle Scholar
  34. 34.
    Ryter, S.W., et al. 2014. The impact of autophagy on cell death modalities. International Journal of Cell Biology 2014: 502676.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Liu, Y., and B. Levine. 2015. Autosis and autophagic cell death: the dark side of autophagy. Cell Death and Differentiation 22 (3): 367–376.PubMedCrossRefGoogle Scholar
  36. 36.
    Aguirre, A., I. López-Alonso, A. González-López, L. Amado-Rodríguez, E. Batalla-Solís, A. Astudillo, J. Blázquez-Prieto, A.F. Fernández, J.A. Galván, C.C. dos Santos, and G.M. Albaiceta. 2014. Defective autophagy impairs ATF3 activity and worsens lung injury during endotoxemia. Journal of Molecular Medicine (Berlin, Germany) 92 (6): 665–676.CrossRefGoogle Scholar
  37. 37.
    Lin, C.W., S. Lo, D.S. Perng, D.B.C. Wu, P.H. Lee, Y.F. Chang, P.L. Kuo, M.L. Yu, S.S.F. Yuan, and Y.C. Hsieh. 2014. Complete activation of autophagic process attenuates liver injury and improves survival in septic mice. Shock 41 (3): 241–249.PubMedCrossRefGoogle Scholar
  38. 38.
    Hsieh, C.H., P.Y. Pai, H.W. Hsueh, S.S. Yuan, and Y.C. Hsieh. 2011. Complete induction of autophagy is essential for cardioprotection in sepsis. Annals of Surgery 253 (6): 1190–1200.PubMedCrossRefGoogle Scholar
  39. 39.
    Unuma, K., T. Aki, T. Funakoshi, K. Hashimoto, and K. Uemura. 2015. Extrusion of mitochondrial contents from lipopolysaccharide-stimulated cells: Involvement of autophagy. Autophagy 11 (9): 1520–1536.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Virgin, H.W., and B. Levine. 2009. Autophagy genes in immunity. Nature Immunology 10 (5): 461–470.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Waltz, P., E.H. Carchman, A.C. Young, J. Rao, M.R. Rosengart, D. Kaczorowski, and B.S. Zuckerbraun. 2011. Lipopolysaccaride induces autophagic signaling in macrophages via a TLR4, heme oxygenase-1 dependent pathway. Autophagy 7 (3): 315–320.PubMedCrossRefGoogle Scholar
  42. 42.
    Carchman, E.H., J. Rao, P.A. Loughran, M.R. Rosengart, and B.S. Zuckerbraun. 2011. Heme oxygenase-1-mediated autophagy protects against hepatocyte cell death and hepatic injury from infection/sepsis in mice. Hepatology 53 (6): 2053–2062.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Tang, Z., L. Ni, S. Javidiparsijani, F. Hu, L. A Gatto, R. Cooney, and G. Wang. 2013. Enhanced liver autophagic activity improves survival of septic mice lacking surfactant proteins A and D. The Tohoku Journal of Experimental Medicine 231 (2): 127–138.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Mei, S., M. Livingston, J. Hao, L. li, C. Mei, and Z. Dong. 2016. Autophagy is activated to protect against endotoxic acute kidney injury. Scientific Reports 6: 22171.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Howell, G.M., H. Gomez, R.D. Collage, P. Loughran, X. Zhang, D.A. Escobar, T.R. Billiar, B.S. Zuckerbraun, and M.R. Rosengart. 2013. Augmenting autophagy to treat acute kidney injury during endotoxemia in mice. PLoS One 8 (7): e69520.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Kaushal, G.P., and S.V. Shah. 2016. Autophagy in acute kidney injury. Kidney International 89 (4): 779–791.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Su, Y., Y. Qu, F.Y. Zhao, H.F. Li, D.Z. Mu, and X.H. Li. 2015. Regulation of autophagy by the nuclear factor κB signaling pathway in the hippocampus of rats with sepsis. Journal of Neuroinflammation 12 (1): 116.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Colell, A., J.E. Ricci, S. Tait, S. Milasta, U. Maurer, L. Bouchier-Hayes, P. Fitzgerald, A. Guio-Carrion, N.J. Waterhouse, C.W. Li, B. Mari, P. Barbry, D.D. Newmeyer, H.M. Beere, and D.R. Green. 2007. GAPDH and autophagy preserve survival after apoptotic cytochrome c release in the absence of caspase activation. Cell 129 (5): 983–997.PubMedCrossRefGoogle Scholar
  49. 49.
    Takaoka, Y., et al. 2014. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) prevents lipopolysaccharide (LPS)-induced, sepsis-related severe acute lung injury in mice. Scientific Reports 4: 5204.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Lo, S., S.S.F. Yuan, C. Hsu, Y.J. Cheng, Y.F. Chang, H.W. Hsueh, P.H. Lee, and Y.C. Hsieh. 2013. Lc3 over-expression improves survival and attenuates lung injury through increasing autophagosomal clearance in septic mice. Annals of Surgery 257 (2): 352–363.PubMedCrossRefGoogle Scholar
  51. 51.
    Tanaka, A., Y. Jin, S.J. Lee, M. Zhang, H.P. Kim, D.B. Stolz, S.W. Ryter, and A.M.K. Choi. 2012. Hyperoxia-induced LC3B interacts with the Fas apoptotic pathway in epithelial cell death. American Journal of Respiratory Cell and Molecular Biology 46 (4): 507–514.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Lee, S.J., S.W. Ryter, J.F. Xu, K. Nakahira, H.P. Kim, A.M.K. Choi, and Y.S. Kim. 2011. Carbon monoxide activates autophagy via mitochondrial reactive oxygen species formation. American Journal of Respiratory Cell and Molecular Biology 45 (4): 867–873.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Green, Douglas R., and B. Levine. 2014. To be or not to be? How selective autophagy and cell death govern cell fate. Cell 157 (1): 65–75.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Chen, H.R., Y.C. Chuang, C.H. Chao, and T.M. Yeh. 2015. Macrophage migration inhibitory factor induces vascular leakage via autophagy. Biology Open 4 (2): 244–252.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Lorne, E., et al. 2009. Participation of mammalian target of rapamycin complex 1 in toll-like receptor 2- and 4-induced neutrophil activation and acute lung injury. American Journal of Respiratory Cell and Molecular Biology 41 (2): 237–245.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Gong, L., R.J. Devenish, and M. Prescott. 2012. Autophagy as a macrophage response to bacterial infection. IUBMB Life 64 (9): 740–747.PubMedCrossRefGoogle Scholar
  57. 57.
    Xu, Y., C. Jagannath, X.D. Liu, A. Sharafkhaneh, K.E. Kolodziejska, and N.T. Eissa. 2007. Toll-like receptor 4 is a sensor for autophagy associated with innate immunity. Immunity 27 (1): 135–144.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Xu, Y., et al. 2014. Signaling pathway of autophagy associated with innate immunity. Autophagy 4 (1): 110–112.CrossRefGoogle Scholar
  59. 59.
    Fujita, K.-I., and S.M. Srinivasula. 2014. TLR4-mediated autophagy in macrophages is a p62-dependent type of selective autophagy of aggresome-like induced structures (ALIS). Autophagy 7 (5): 552–554.CrossRefGoogle Scholar
  60. 60.
    Harris, J., M. Hartman, C. Roche, S.G. Zeng, A. O'Shea, F.A. Sharp, E.M. Lambe, E.M. Creagh, D.T. Golenbock, J. Tschopp, H. Kornfeld, K.A. Fitzgerald, and E.C. Lavelle. 2011. Autophagy controls IL-1beta secretion by targeting pro-IL-1beta for degradation. The Journal of Biological Chemistry 286 (11): 9587–9597.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Ko, J., et al. 2017. Rapamycin regulates macrophage activation by inhibiting NLRP3 inflammasome-p38 MAPK-NFκB pathways in autophagy- and p62-dependent manners. Oncotarget 8: 40817–40831.PubMedPubMedCentralGoogle Scholar
  62. 62.
    Lee, J.P., et al. 2016. Loss of autophagy enhances MIF/macrophage migration inhibitory factor release by macrophages. Autophagy 12 (6): 907–916.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Chuang, Y.C., W.H. Su, H.Y. Lei, Y.S. Lin, H.S. Liu, C.P. Chang, and T.M. Yeh. 2012. Macrophage migration inhibitory factor induces autophagy via reactive oxygen species generation. PLoS One 7 (5): e37613.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Zhang, Y., M.J. Morgan, K. Chen, S. Choksi, and Z.G. Liu. 2012. Induction of autophagy is essential for monocyte-macrophage differentiation. Blood 119 (12): 2895–2905.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Geissmann, F., et al. 2010. Development of monocytes, macrophages, and dendritic cells. Science 327 (5966): 656–661.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Boulakirba, S., et al. 2018. IL-34 and CSF-1 display an equivalent macrophage differentiation ability but a different polarization potential. Scientific Reports 8 (1):256.Google Scholar
  67. 67.
    Jacquel, A., S. Obba, L. Boyer, M. Dufies, G. Robert, P. Gounon, E. Lemichez, F. Luciano, E. Solary, and P. Auberger. 2012. Autophagy is required for CSF-1-induced macrophagic differentiation and acquisition of phagocytic functions. Blood 119 (19): 4527–4531.PubMedCrossRefGoogle Scholar
  68. 68.
    Jacquel, A., et al. 2014. Proper macrophagic differentiation requires both autophagy and caspase activation. Autophagy 8 (7): 1141–1143.CrossRefGoogle Scholar
  69. 69.
    Mizushima, N., and B. Levine. 2010. Autophagy in mammalian development and differentiation. Nature Cell Biology 12 (9): 823–830.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Colosetti, P., et al. 2014. Autophagy is an important event for megakaryocytic differentiation of the chronic myelogenous leukemia K562 cell line. Autophagy 5 (8): 1092–1098.CrossRefGoogle Scholar
  71. 71.
    Mortensen, M., D.J.P. Ferguson, M. Edelmann, B. Kessler, K.J. Morten, M. Komatsu, and A.K. Simon. 2010. Loss of autophagy in erythroid cells leads to defective removal of mitochondria and severe anemia in vivo. Proceedings of the National Academy of Sciences of the United States of America 107 (2): 832–837.PubMedCrossRefGoogle Scholar
  72. 72.
    da Silva, B.J., et al. 2014. Physalis angulata induces in vitro differentiation of murine bone marrow cells into macrophages. BMC Cell Biology 15: 37–48.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Sun, K.T., et al. 2015. MicroRNA-20a regulates autophagy related protein-ATG16L1 in hypoxia-induced osteoclast differentiation. Bone 73: 145–153.PubMedCrossRefGoogle Scholar
  74. 74.
    Singh, A., and E. Sen. 2017. Reciprocal role of SIRT6 and hexokinase 2 in the regulation of autophagy driven monocyte differentiation. Experimental Cell Research 360 (2): 365–374.PubMedCrossRefGoogle Scholar
  75. 75.
    Chen, P., M. Cescon, and P. Bonaldo. 2014. Autophagy-mediated regulation of macrophages and its applications for cancer. Autophagy 10 (2): 192–200.PubMedCrossRefGoogle Scholar
  76. 76.
    Droin, N., et al. 2010. Alpha-defensins secreted by dysplastic granulocytes inhibit the differentiation of monocytes in chronic myelomonocytic leukemia. Blood 115: 78–88.PubMedCrossRefGoogle Scholar
  77. 77.
    Obba, S., Z. Hizir, L. Boyer, D. Selimoglu-Buet, A. Pfeifer, G. Michel, M.A. Hamouda, D. Gonçalvès, M. Cerezo, S. Marchetti, S. Rocchi, N. Droin, T. Cluzeau, G. Robert, F. Luciano, B. Robaye, M. Foretz, B. Viollet, L. Legros, E. Solary, P. Auberger, and A. Jacquel. 2015. The PRKAA1/AMPKα1 pathway triggers autophagy during CSF1-induced human monocyte differentiation and is a potential target in CMML. Autophagy 11 (7): 1114–1129.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Tarique, A.A., et al. 2015. Phenotypic, functional, and plasticity features of classical and alternatively activated human macrophages. American Journal of Respiratory Cell and Molecular Biology 53: 1–45.CrossRefGoogle Scholar
  79. 79.
    Gordon, S., and F.O. Martinez. 2010. Alternative activation of macrophages: mechanism and functions. Immunity 32 (5): 593–604.PubMedCrossRefGoogle Scholar
  80. 80.
    Ip, W.K.E., et al. 2017. Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages. Science 356: 513–519.PubMedCrossRefGoogle Scholar
  81. 81.
    Yang, M., J. Liu, J. Shao, Y. Qin, Q. Ji, X. Zhang, and J. du. 2014. Cathepsin S-mediated autophagic flux in tumor-associated macrophages accelerate tumor development by promoting M2 polarization. Molecular Cancer 13: 43.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Gauthier, A., and M. Ho. 2013. Role of sorafenib in the treatment of advanced hepatocellular carcinoma: an update. Hepatology Research 43 (2): 147–154.PubMedCrossRefGoogle Scholar
  83. 83.
    Chang, C.P., Y.C. Su, P.H. Lee, and H.Y. Lei. 2013. Targeting NFKB by autophagy to polarize hepatoma-associated macrophage differentiation. Autophagy 9 (4): 619–621.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Chang, C.P., Y.C. Su, C.W. Hu, and H.Y. Lei. 2013. TLR2-dependent selective autophagy regulates NF-kappaB lysosomal degradation in hepatoma-derived M2 macrophage differentiation. Cell Death and Differentiation 20 (3): 515–523.PubMedCrossRefGoogle Scholar
  85. 85.
    Rocher, C., and D.K. Singla. 2013. SMAD-PI3K-Akt-mTOR pathway mediates BMP-7 polarization of monocytes into M2 macrophages. PLoS One 8 (12): e84009.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Chen, W., T. Ma, X.N. Shen, X.F. Xia, G.D. Xu, X.L. Bai, and T.B. Liang. 2012. Macrophage-induced tumor angiogenesis is regulated by the TSC2-mTOR pathway. Cancer Research 72 (6): 1363–1372.PubMedCrossRefGoogle Scholar
  87. 87.
    Vergadi, E., E. Ieronymaki, K. Lyroni, K. Vaporidi, and C. Tsatsanis. 2017. Akt signaling pathway in macrophage activation and M1/M2 polarization. Journal of Immunology 198 (3): 1006–1014.CrossRefGoogle Scholar
  88. 88.
    Hu, R., Z.F. Chen, J. Yan, Q.F. Li, Y. Huang, H. Xu, X. Zhang, and H. Jiang. 2014. Complement C5a exacerbates acute lung injury induced through autophagy-mediated alveolar macrophage apoptosis. Cell Death & Disease 5: e1330.CrossRefGoogle Scholar
  89. 89.
    Descloux, C., V. Ginet, P.G.H. Clarke, J. Puyal, and A.C. Truttmann. 2015. Neuronal death after perinatal cerebral hypoxia-ischemia: focus on autophagy-mediated cell death. International Journal of Developmental Neuroscience 45: 75–85.PubMedCrossRefGoogle Scholar
  90. 90.
    Li, S., L. Guo, P. Qian, Y. Zhao, A. Liu, F. Ji, L. Chen, X. Wu, and G. Qian. 2015. Lipopolysaccharide induces autophagic cell death through the PERK-dependent branch of the unfolded protein response in human alveolar epithelial A549 cells. Cellular Physiology and Biochemistry 36 (6): 2403–2417.PubMedCrossRefGoogle Scholar
  91. 91.
    Zhang, Y., Y. Liu, and J. Zhang. 2015. Saturated hydrogen saline attenuates endotoxin-induced lung dysfunction. The Journal of Surgical Research 198 (1): 41–49.PubMedCrossRefGoogle Scholar
  92. 92.
    Zhang, L., et al. 2012. Interferon regulatory factor-1 regulates the autophagic response in LPS-stimulated macrophages through nitric oxide. Molecular Medicine 18: 201–208.PubMedCrossRefGoogle Scholar
  93. 93.
    Pattingre, S., A. Tassa, X. Qu, R. Garuti, X.H. Liang, N. Mizushima, M. Packer, M.D. Schneider, and B. Levine. 2005. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 122: 927–939.PubMedCrossRefGoogle Scholar
  94. 94.
    Mariño, G., M. Niso-Santano, E.H. Baehrecke, and G. Kroemer. 2014. Self-consumption: the interplay of autophagy and apoptosis. Nature Reviews Molecular Cell Biology 15 (2): 81–94.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Yousefi, S., R. Perozzo, I. Schmid, A. Ziemiecki, T. Schaffner, L. Scapozza, T. Brunner, and H.U. Simon. 2006. Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nature Cell Biology 8 (10): 1124–1132.PubMedCrossRefGoogle Scholar
  96. 96.
    Rubinstein, Assaf D., Miriam Eisenstein, Yaara Ber, Shani Bialik, and Adi Kimchi. 2011. The autophagy protein Atg12 associates with antiapoptotic Bcl-2 family members to promote mitochondrial apoptosis. Molecular Cell 44 (5): 698–709.PubMedCrossRefGoogle Scholar
  97. 97.
    Byrne, B.G., et al. 2013. Inflammasome components coordinate autophagy and pyroptosis as macrophage responses to infection. MBio 4 (1): e00620–e00612.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Fimia, G.M., et al. 2012. Autophagy suppresses RIP kinase-dependent necrosis enabling survival to mTOR inhibition. PLoS One 7 (7):e41831.Google Scholar
  99. 99.
    Periyasamy-Thandavan, S., M. Jiang, Q. Wei, R. Smith, X.M. Yin, and Z. Dong. 2008. Autophagy is cytoprotective during cisplatin injury of renal proximal tubular cells. Kidney International 74 (5): 631–640.PubMedCrossRefGoogle Scholar
  100. 100.
    Yang, C., V. Kaushal, S.V. Shah, and G.P. Kaushal. 2008. Autophagy is associated with apoptosis in cisplatin injury to renal tubular epithelial cells. American Journal of Physiology. Renal Physiology 294 (4): F777–F787.PubMedCrossRefGoogle Scholar
  101. 101.
    Kaushal, G.P., V. Kaushal, C. Herzog, and C. Yang. 2008. Autophagy delays apoptosis in renal tubular epithelial cells in cisplatin cytotoxicity. Autophagy 4: 710–712.PubMedCrossRefGoogle Scholar
  102. 102.
    Herzog, C., C. Yang, A. Holmes, and G.P. Kaushal. 2012. zVAD-fmk prevents cisplatin-induced cleavage of autophagy proteins but impairs autophagic flux and worsens renal function. American Journal of Physiology. Renal Physiology 303 (8): F1239–F1250.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Stranks, A.J., A.L. Hansen, I. Panse, M. Mortensen, D.J.P. Ferguson, D.J. Puleston, K. Shenderov, A.S. Watson, M. Veldhoen, K. Phadwal, V. Cerundolo, and A.K. Simon. 2015. Autophagy controls acquisition of aging features in macrophages. Journal of Innate Immunity 7 (4): 375–391.PubMedCrossRefGoogle Scholar
  104. 104.
    Matsuzawa, T., E. Fujiwara, and Y. Washi. 2014. Autophagy activation by interferon-gamma via the p38 mitogen-activated protein kinase signalling pathway is involved in macrophage bactericidal activity. Immunology 141 (1): 61–69.PubMedCrossRefGoogle Scholar
  105. 105.
    Li, W., S. Zhu, J. Li, A. Assa, A. Jundoria, J. Xu, S. Fan, N.T. Eissa, K.J. Tracey, A.E. Sama, and H. Wang. 2011. EGCG stimulates autophagy and reduces cytoplasmic HMGB1 levels in endotoxin-stimulated macrophages. Biochemical Pharmacology 81 (9): 1152–1163.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Xia, H., L. Chen, H. Liu, Z. Sun, W. Yang, Y. Yang, S. Cui, S. Li, Y. Wang, L. Song, A.F. Abdelgawad, Y. Shang, and S. Yao. 2017. Protectin DX increases survival in a mouse model of sepsis by ameliorating inflammation and modulating macrophage phenotype. Scientific Reports 7 (1): 99.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Williams-Bey, Y., C. Boularan, A. Vural, N.N. Huang, I.Y. Hwang, C. Shan-Shi, and J.H. Kehrl. 2014. Omega-3 free fatty acids suppress macrophage inflammasome activation by inhibiting NF-kappaB activation and enhancing autophagy. PLoS One 9 (6): e97957.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Abdulnour, R.E., et al. 2014. Maresin 1 biosynthesis during platelet-neutrophil interactions is organ-protective. Proceedings of the National Academy of Sciences of the United States of America 111 (46): 16526–16531.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Lin, J., et al. 2017. Maresin-1 activates autophagy in macrophages via ALX/NF-κB pathway. Journal of Wenzhou Medical University 47: 474–479.Google Scholar
  110. 110.
    Li, X.J., et al. 2014. Effect of moxibustion on autophagy of macrophages in mice. Hubei Journal of TCM 36: 19–20.CrossRefGoogle Scholar
  111. 111.
    Yu, H.H., et al. 2016. Effects of Huang-Lian-Jie-Du-Decotion containing serum on expressions of autophagy related gene in macrophages. Chinese Journal of Immunology 32: 1150–1164.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of AnesthesiologyShengjing Hospital of China Medical UniversityShenyangPeople’s Republic of China
  2. 2.Department of OncologyShengjing Hospital of China Medical UniversityShenyangPeople’s Republic of China

Personalised recommendations