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Neutrophil ALDH2 is a new therapeutic target for the effective treatment of sepsis-induced ARDS

Cellular & Molecular Immunology (2024)Cite this article

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Abstract

Acetaldehyde dehydrogenase 2 (ALDH2) mutations are commonly found in a subgroup of the Asian population. However, the role of ALDH2 in septic acute respiratory distress syndrome (ARDS) remains unknown. Here, we showed that human subjects carrying the ALDH2rs671 mutation were highly susceptible to developing septic ARDS. Intriguingly, ALDH2rs671-ARDS patients showed higher levels of blood cell-free DNA (cfDNA) and myeloperoxidase (MPO)-DNA than ALDH2WT-ARDS patients. To investigate the mechanisms underlying ALDH2 deficiency in the development of septic ARDS, we utilized Aldh2 gene knockout mice and Aldh2rs671 gene knock-in mice. In clinically relevant mouse sepsis models, Aldh2-/- mice and Aldh2rs671 mice exhibited pulmonary and circulating NETosis, a specific process that releases neutrophil extracellular traps (NETs) from neutrophils. Furthermore, we discovered that NETosis strongly promoted endothelial destruction, accelerated vascular leakage, and exacerbated septic ARDS. At the molecular level, ALDH2 increased K48-linked polyubiquitination and degradation of peptidylarginine deiminase 4 (PAD4) to inhibit NETosis, which was achieved by promoting PAD4 binding to the E3 ubiquitin ligase CHIP. Pharmacological administration of the ALDH2-specific activator Alda-1 substantially alleviated septic ARDS by inhibiting NETosis. Together, our data reveal a novel ALDH2-based protective mechanism against septic ARDS, and the activation of ALDH2 may be an effective treatment strategy for sepsis.

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References

  1. Bos LDJ, Ware LB. Acute respiratory distress syndrome: causes, pathophysiology, and phenotypes. Lancet. 2022;400:1145–56.

    Article  PubMed  Google Scholar 

  2. ARDS Definition Task Force, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307:2526–33.

    Google Scholar 

  3. Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016;315:788–800.

    Article  CAS  PubMed  Google Scholar 

  4. Fan E, Brodie D, Slutsky AS. Acute respiratory distress syndrome: advances in diagnosis and treatment. JAMA. 2018;319:698–710.

    Article  PubMed  Google Scholar 

  5. Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, et al. Incidence and outcomes of acute lung injury. N. Engl J Med. 2005;353:1685–93.

    Article  CAS  PubMed  Google Scholar 

  6. Joffre J, Hellman J, Ince C, Ait-Oufella H. Endothelial responses in sepsis. Am J Respir Crit Care Med. 2020;202:361–70.

    Article  CAS  PubMed  Google Scholar 

  7. Jaffee W, Hodgins S, McGee WT. Tissue Edema, fluid balance, and patient outcomes in severe sepsis: an organ systems review. J Intensive Care Med. 2018;33:502–9.

    Article  PubMed  Google Scholar 

  8. Chang R, Holcomb JB. Choice of fluid therapy in the initial management of sepsis, severe sepsis, and septic shock. Shock. 2016;46:17–26.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Zhang J, Guo Y, Zhao X, Pang J, Pan C, Wang J, et al. The role of aldehyde dehydrogenase 2 in cardiovascular disease. Nat Rev Cardiol. 2023;20:495–509.

    Article  PubMed  Google Scholar 

  10. Zhang J, Zhao X, Guo Y, Liu Z, Wei S, Yuan Q, et al. Macrophage ALDH2 (Aldehyde Dehydrogenase 2) stabilizing Rac2 is required for efferocytosis internalization and reduction of atherosclerosis development. Arterioscler Thromb Vasc Biol. 2022;42:700–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Zhang Y, Lv Y, Zhang Q, Wang X, Han Q, Liang Y, et al. ALDH2 attenuates myocardial pyroptosis through breaking down Mitochondrion-NLRP3 inflammasome pathway in septic shock. Front Pharm. 2023;14:1125866.

    Article  CAS  Google Scholar 

  12. Millwood IY, Walters RG, Mei XW, Guo Y, Yang L, Bian Z, et al. Conventional and genetic evidence on alcohol and vascular disease aetiology: a prospective study of 500 000 men and women in China. Lancet. 2019;393:1831–42.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Chen CH, Ferreira JC, Gross ER, Mochly-Rosen D. Targeting aldehyde dehydrogenase 2: new therapeutic opportunities. Physiol Rev. 2014;94:1–34.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Hsu LA, Tsai FC, Yeh YH, Chang CJ, Kuo CT, Chen WJ, et al. Aldehyde Dehydrogenase 2 ameliorates chronic alcohol consumption-induced atrial fibrillation through detoxification of 4-HNE. Int J Mol Sci. 2020;21:6678.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  15. Chang JS, Hsiao JR, Chen CH. ALDH2 polymorphism and alcohol-related cancers in Asians: a public health perspective. J Biomed Sci. 2017;24:19.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Perez-Miller S, Younus H, Vanam R, Chen CH, Mochly-Rosen D, Hurley TD. Alda-1 is an agonist and chemical chaperone for the common human aldehyde dehydrogenase 2 variant. Nat Struct Mol Biol. 2010;17:159–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Sidramagowda Patil S, Hernández-Cuervo H, Fukumoto J, Krishnamurthy S, Lin M, Alleyn M, et al. Alda-1 attenuates hyperoxia-induced acute lung injury in mice. Front Pharm. 2020;11:597942.

    Article  Google Scholar 

  18. Kuroda A, Hegab AE, Jingtao G, Yamashita S, Hizawa N, Sakamoto T, et al. Effects of the common polymorphism in the human aldehyde dehydrogenase 2 (ALDH2) gene on the lung. Respir Res. 2017;18:69.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Oka Y, Hamada M, Nakazawa Y, Muramatsu H, Okuno Y, Higasa K, et al. Digenic mutations in ALDH2 and ADH5 impair formaldehyde clearance and cause a multisystem disorder, AMeD syndrome. Sci Adv. 2020;6:eabd7197.

    Article  ADS  CAS  PubMed  Google Scholar 

  20. Hu Y, Yan JB, Zheng MZ, Song XH, Wang LL, Shen YL, et al. Mitochondrial aldehyde dehydrogenase activity protects against lipopolysaccharide‑induced cardiac dysfunction in rats. Mol Med Rep. 2015;11:1509–15.

    Article  CAS  PubMed  Google Scholar 

  21. Pang J, Zheng Y, Han Q, Zhang Y, Sun R, Wang J, et al. The role of ALDH2 in sepsis and the to-be-discovered mechanisms. Adv Exp Med Biol. 2019;1193:175–94.

    Article  CAS  PubMed  Google Scholar 

  22. Mantovani A, Cassatella MA, Costantini C, Jaillon S. Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol. 2011;11:519–31.

    Article  CAS  PubMed  Google Scholar 

  23. Liew PX, Kubes P. The neutrophil’s role during health and disease. Physiol Rev. 2019;99:1223–48.

    Article  CAS  PubMed  Google Scholar 

  24. Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, et al. Neutrophil extracellular traps kill bacteria. Science. 2004;303:1532–5.

    Article  ADS  CAS  PubMed  Google Scholar 

  25. Fuchs TA, Abed U, Goosmann C, Hurwitz R, Schulze I, Wahn V, et al. Novel cell death program leads to neutrophil extracellular traps. J Cell Biol. 2007;176:231–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Yipp BG, Kubes P. NETosis: how vital is it? Blood. 2013;122:2784–94.

    Article  CAS  PubMed  Google Scholar 

  27. Thiam HR, Wong SL, Wagner DD, Waterman CM. Cellular Mechanisms of NETosis. Annu Rev Cell Dev Biol. 2020;36:191–218.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Chen L, Zhao Y, Lai D, Zhang P, Yang Y, Li Y, et al. Neutrophil extracellular traps promote macrophage pyroptosis in sepsis. Cell Death Dis. 2018;9:597.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Perdomo J, Leung H, Ahmadi Z, Yan F, Chong J, Passam FH, et al. Neutrophil activation and NETosis are the major drivers of thrombosis in heparin-induced thrombocytopenia. Nat Commun. 2019;10:1322.

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  30. Mattox AK, Douville C, Wang Y, Popoli M, Ptak J, Silliman N, et al. The origin of highly elevated cell-free DNA in healthy individuals and patients with pancreatic, colorectal, lung, or ovarian cancer. Cancer Discov. 2023;13:2166–2179.

    Article  PubMed  Google Scholar 

  31. Thiam HR, Wong SL, Qiu R, Kittisopikul M, Vahabikashi A, Goldman AE, et al. NETosis proceeds by cytoskeleton and endomembrane disassembly and PAD4-mediated chromatin decondensation and nuclear envelope rupture. Proc Natl Acad Sci USA. 2020;117:7326–37.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  32. Neubert E, Meyer D, Rocca F, Günay G, Kwaczala-Tessmann A, Grandke J, et al. Chromatin swelling drives neutrophil extracellular trap release. Nat Commun. 2018;9:3767.

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  33. Li P, Li M, Lindberg MR, Kennett MJ, Xiong N, Wang Y. PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps. J Exp Med. 2010;207:1853–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Martinod K, Demers M, Fuchs TA, Wong SL, Brill A, Gallant M, et al. Neutrophil histone modification by peptidylarginine deiminase 4 is critical for deep vein thrombosis in mice. Proc Natl Acad Sci USA. 2013;110:8674–9.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  35. Biron BM, Chung CS, Chen Y, Wilson Z, Fallon EA, Reichner JS, et al. PAD4 deficiency leads to decreased organ dysfunction and improved survival in a dual insult model of hemorrhagic shock and sepsis. J Immunol. 2018;200:1817–28.

    Article  CAS  PubMed  Google Scholar 

  36. Alsabani M, Abrams ST, Cheng Z, Morton B, Lane S, Alosaimi S, et al. Reduction of NETosis by targeting CXCR1/2 reduces thrombosis, lung injury, and mortality in experimental human and murine sepsis. Br J Anaesth. 2022;128:283–93.

    Article  CAS  PubMed  Google Scholar 

  37. Pham T, Rubenfeld GD. Fifty years of research in ARDS. The epidemiology of acute respiratory distress syndrome. a 50th birthday review. Am J Respir Crit Care Med. 2017;195:860–70.

    Article  PubMed  Google Scholar 

  38. Rezoagli E, Fumagalli R, Bellani G. Definition and epidemiology of acute respiratory distress syndrome. Ann Transl Med. 2017;5:282.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Matthay MA, Zemans RL, Zimmerman GA, Arabi YM, Beitler JR, Mercat A, et al. Acute respiratory distress syndrome. Nat Rev Dis Prim. 2019;5:18.

    Article  PubMed  Google Scholar 

  40. Parotto M, Gyöngyösi M, Howe K, Myatra SN, Ranzani O, Shankar-Hari M, et al. Post-acute sequelae of COVID-19: understanding and addressing the burden of multisystem manifestations. Lancet Respir Med. 2023;11:739–54.

    Article  PubMed  Google Scholar 

  41. Carmona-Rivera C, Zhao W, Yalavarthi S, Kaplan MJ. Neutrophil extracellular traps induce endothelial dysfunction in systemic lupus erythematosus through the activation of matrix metalloproteinase-2. Ann Rheum Dis. 2015;74:1417–24.

    Article  CAS  PubMed  Google Scholar 

  42. Kato N, Takeuchi F, Tabara Y, Kelly TN, Go MJ, Sim X, et al. Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians. Nat Genet. 2011;43:531–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ma H, Guo R, Yu L, Zhang Y, Ren J. Aldehyde dehydrogenase 2 (ALDH2) rescues myocardial ischaemia/reperfusion injury: role of autophagy paradox and toxic aldehyde. Eur Heart J. 2011;32:1025–38.

    Article  CAS  PubMed  Google Scholar 

  44. Dingler FA, Wang M, Mu A, Millington CL, Oberbeck N, Watcham S, et al. Two aldehyde clearance systems are essential to prevent lethal formaldehyde accumulation in mice and humans. Mol Cell. 2020;80:996–1012.e9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Liu H, Hu Q, Ren K, Wu P, Wang Y, Lv C. ALDH2 mitigates LPS-induced cardiac dysfunction, inflammation, and apoptosis through the cGAS/STING pathway. Mol Med. 2023;29:171.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Jin J, Chang RS, Xu S, Xia G, Wong J, Fang Y, et al. Aldehyde Dehydrogenase 2 ameliorates LPS-induced acute kidney injury through detoxification of 4-HNE and suppression of the MAPK pathway. J Immunol Res. 2023;2023:5513507.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Ji W, Wan T, Zhang F, Zhu X, Guo S, Mei X. Aldehyde Dehydrogenase 2 protects against lipopolysaccharide-induced myocardial injury by suppressing mitophagy. Front Pharm. 2021;12:641058.

    Article  CAS  Google Scholar 

  48. Ning L, Wei W, Wenyang J, Rui X, Qing G. Cytosolic DNA-STING-NLRP3 axis is involved in murine acute lung injury induced by lipopolysaccharide. Clin Transl Med. 2020;10:e228.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Rittirsch D, Huber-Lang MS, Flierl MA, Ward PA. Immunodesign of experimental sepsis by cecal ligation and puncture. Nat Protoc. 2009;4:31–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Ho J, Chan H, Liang Y, Liu X, Zhang L, Li Q, et al. Cathelicidin preserves intestinal barrier function in polymicrobial sepsis. Crit Care. 2020;24:47.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Han S, Lee SJ, Kim KE, Lee HS, Oh N, Park I, et al. Amelioration of sepsis by TIE2 activation-induced vascular protection. Sci Transl Med. 2016;8:335ra55.

    Article  PubMed  Google Scholar 

  52. Peng X, Hassoun PM, Sammani S, McVerry BJ, Burne MJ, Rabb H, et al. Protective effects of sphingosine 1-phosphate in murine endotoxin-induced inflammatory lung injury. Am J Respir Crit Care Med. 2004;169:1245–51.

    Article  PubMed  Google Scholar 

  53. Kulkarni HS, Lee JS, Bastarache JA, Kuebler WM, Downey GP, Albaiceta GM, et al. Update on the features and measurements of experimental acute lung injury in animals: An Official American Thoracic Society Workshop Report. Am J Respir Cell Mol Biol. 2022;66:e1–e14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Jin H, Aziz M, Murao A, Kobritz M, Shih AJ, Adelson RP, et al. Antigen-presenting aged neutrophils induce CD4+ T cells to exacerbate inflammation in sepsis. J Clin Invest. 2023;133:e164585.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kim B, Jang C, Dharaneeswaran H, Li J, Bhide M, Yang S, et al. Endothelial pyruvate kinase M2 maintains vascular integrity. J Clin Invest. 2018;128:4543–56.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Newman AM, Bratman SV, To J, Wynne JF, Eclov NC, Modlin LA, et al. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat Med. 2014;20:548–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Middleton EA, He XY, Denorme F, Campbell RA, Ng D, Salvatore SP, et al. Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome. Blood. 2020;136:1169–79.

    Article  CAS  PubMed  Google Scholar 

  58. Najmeh, S, Cools-Lartigue J, Giannias B, Spicer J, Ferri LE, Simplified Human Neutrophil Extracellular Traps (NETs) Isolation and Handling. J Vis Exp. 2015;98:52687.

  59. Deng M, Tang Y, Li W, Wang X, Zhang R, Zhang X, et al. The endotoxin delivery protein HMGB1 mediates Caspase-11-dependent lethality in sepsis. Immunity. 2018;49:740–753.e7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study was supported by the State Key Program of the National Natural Science Foundation of China (82030059), the National Science Fund for Distinguished Young Scholars (82325031), the National Natural Science Regional Innovation Fund Joint Fund Key Support Projects (U23A20485), the National Natural Science Foundation of China (82072144, 82172127), the National Key R&D Program of China (2020YFC1512700, 2020YFC1512705, 2020YFC1512703), the Key R&D Program of Shandong Province (2021ZLGX02, 2021SFGC0503, 2022ZLGX03), the Taishan Pandeng Scholar Program of Shandong Province (tspd20181220), the Taishan Young Scholar Program of Shandong Province (tsqn202211312), the Clinical Research Project of Shandong University (2021SDUCRCC006), and the Interdisciplinary Young Researcher Groups Program of Shandong University (2020QNQT004). Illustrations were made using BioRender.

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  1. These authors contributed equally: Changchang Xu, Lin Zhang.

Authors and Affiliations

  1. Department of Emergency Medicine, Qilu Hospital of Shandong University, Jinan, China

    Changchang Xu, Lin Zhang, Shaoyu Xu, Zichen Wang, Qi Han, Ying Lv, Xingfang Wang, Xiangxin Zhang, Qingju Zhang, Ying Zhang, Simeng He, Qiuhuan Yuan, Yuan Bian, Chuanbao Li, Jiali Wang, Feng Xu, Jiaojiao Pang & Yuguo Chen

  2. Chest Pain Center, Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, China

    Changchang Xu, Lin Zhang, Shaoyu Xu, Zichen Wang, Qi Han, Ying Lv, Xingfang Wang, Xiangxin Zhang, Qingju Zhang, Ying Zhang, Simeng He, Qiuhuan Yuan, Yuan Bian, Chuanbao Li, Jiali Wang, Feng Xu, Jiaojiao Pang & Yuguo Chen

  3. Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China

    Changchang Xu, Lin Zhang, Shaoyu Xu, Zichen Wang, Qi Han, Ying Lv, Xingfang Wang, Xiangxin Zhang, Qingju Zhang, Ying Zhang, Simeng He, Qiuhuan Yuan, Yuan Bian, Chuanbao Li, Jiali Wang, Feng Xu, Jiaojiao Pang & Yuguo Chen

  4. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China

    Changchang Xu, Lin Zhang, Shaoyu Xu, Zichen Wang, Qi Han, Ying Lv, Xingfang Wang, Xiangxin Zhang, Qingju Zhang, Ying Zhang, Simeng He, Qiuhuan Yuan, Yuan Bian, Chuanbao Li, Jiali Wang, Feng Xu, Jiaojiao Pang & Yuguo Chen

  5. Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, 171 65, Sweden

    Yihai Cao

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  1. Changchang Xu
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Contributions

Y Chen and JP conceived and designed the experiments. CX and LZ performed most of the experiments with the help of SX, ZW, QH, YL, XW, XZ, QZ, YZ, SH, and QY CX, LZ, SX, ZW, and YB performed the data analysis. Y Cao and JP assisted in revising the draft. CL, JW, and FX provided valuable experimental advice and guidance. All authors have read and approved the final manuscript.

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Correspondence to Jiaojiao Pang or Yuguo Chen.

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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.

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Xu, C., Zhang, L., Xu, S. et al. Neutrophil ALDH2 is a new therapeutic target for the effective treatment of sepsis-induced ARDS. Cell Mol Immunol (2024). https://doi.org/10.1038/s41423-024-01146-w

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