Identification of Neutrophil Extracellular Trap-Related Gene Expression Signatures in Ischemia Reperfusion Injury During Lung Transplantation: A Transcriptome Analysis and Clinical Validation

References

• Schaffer JM, Singh SK, Reitz BA, Zamanian RT, Mallidi HR. Single- vs double-lung transplantation in patients with chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis since the implementation of lung allocation based on medical need. JAMA. 2015;313(9):936–948. doi:10.1001/jama.2015.1175
   PubMed Web of Science ®Google Scholar
• Lahzami S, Bridevaux PO, Soccal PM, et al. Survival impact of lung transplantation for COPD. Eur Respir J. 2010;36(1):74–80. doi:10.1183/09031936.00087809
   PubMed Web of Science ®Google Scholar
• Toronto Lung Transplant Group*. Unilateral lung transplantation for pulmonary fibrosis. New Engl J Med. 1986;314(18):1140–1145. doi:10.1056/nejm198605013141802
   PubMed Web of Science ®Google Scholar
• Chambers DC, Cherikh WS, Harhay MO, et al. The International Thoracic Organ Transplant Registry of the International Society for heart and lung transplantation: thirty-sixth adult lung and heart-lung transplantation report-2019; focus theme: donor and recipient size match. J Heart Lung Transplant. 2019;38(10):1042–1055. doi:10.1016/j.healun.2019.08.001
   PubMedGoogle Scholar
• Shepherd HM, Gauthier JM, Li W, Krupnick AS, Gelman AE, Kreisel D. Innate immunity in lung transplantation. J Heart Lung Transplant. 2021;40(7):562–568. doi:10.1016/j.healun.2021.03.017
   PubMed Web of Science ®Google Scholar
• Capuzzimati M, Hough O, Liu M. Cell death and ischemia-reperfusion injury in lung transplantation. J Heart Lung Transplant. 2022;41(8):1003–1013. doi:10.1016/j.healun.2022.05.013
   PubMed Web of Science ®Google Scholar
• Chen-Yoshikawa TF. Ischemia-reperfusion injury in lung transplantation. Cells. 2021;10(6). doi:10.3390/cells10061333
   PubMed Web of Science ®Google Scholar
• Grimm JC, Valero V, Kilic A, et al. Association between prolonged graft ischemia and primary graft failure or survival following lung transplantation. JAMA Surgery. 2015;150(6):547–553. doi:10.1001/jamasurg.2015.12
   PubMed Web of Science ®Google Scholar
• Kreisel D, Krupnick AS, Puri V, et al. Short- and long-term outcomes of 1000 adult lung transplant recipients at a single center. J Thoracic Cardiovasc Surg. 2011;141(1):215–222. doi:10.1016/j.jtcvs.2010.09.009
   PubMed Web of Science ®Google Scholar
• Li W, Terada Y, Tyurina YY, et al. Necroptosis triggers spatially restricted neutrophil-mediated vascular damage during lung ischemia reperfusion injury. Proc Natl Acad Sci USA. 2022;119(10):e2111537119. doi:10.1073/pnas.2111537119
   PubMed Web of Science ®Google Scholar
• Meyer KC, Nunley DR, Dauber JH, et al. Neutrophils, Unopposed Neutrophil Elastase, and Alpha 1-Antiprotease defenses following human lung transplantation. Am J Respir Crit Care Med. 2001;164(1):97–102. doi:10.1164/ajrccm.164.1.2006096
   PubMed Web of Science ®Google Scholar
• Gelman AE, Fisher AJ, Huang HJ, et al. Report of the ISHLT Working Group on Primary Lung Graft Dysfunction Part III: mechanisms: a 2016 Consensus Group Statement of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2017;36(10):1114–1120. doi:10.1016/j.healun.2017.07.014
   PubMed Web of Science ®Google Scholar
• Jorch SK, Kubes P. An emerging role for neutrophil extracellular traps in noninfectious disease. Nature Med. 2017;23(3):279–287. doi:10.1038/nm.4294
   PubMed Web of Science ®Google Scholar
• Campos J, Ponomaryov T, De Prendergast A, et al. Neutrophil extracellular traps and inflammasomes cooperatively promote venous thrombosis in mice. Blood Adv. 2021;5(9):2319–2324. doi:10.1182/bloodadvances.2020003377
   PubMed Web of Science ®Google Scholar
• Sharma S, Hofbauer TM, Ondracek AS, et al. Neutrophil extracellular traps promote fibrous vascular occlusions in chronic thrombosis. Blood. 2021;137(8):1104–1116. doi:10.1182/blood.2020005861
   PubMed Web of Science ®Google Scholar
• Bonneau S, Landry C, Bégin S, et al. Correlation between Neutrophil Extracellular Traps (NETs) expression and primary graft dysfunction following human lung transplantation. Cells. 2022;11(21). doi:10.3390/cells11213420
   PubMed Web of Science ®Google Scholar
• Sayah DM, Mallavia B, Liu F, et al. Neutrophil extracellular traps are pathogenic in primary graft dysfunction after lung transplantation. Am J Respir Crit Care Med. 2015;191(4):455–463. doi:10.1164/rccm.201406-1086OC
   PubMed Web of Science ®Google Scholar
• Baciu C, Shin J, Hsin M, Cypel M, Keshavjee S, Liu M. Altered purine metabolism at reperfusion affects clinical outcome in lung transplantation. Thorax. 2023;78(3):249–257. doi:10.1136/thoraxjnl-2021-217498
   PubMed Web of Science ®Google Scholar
• Wong A, Zamel R, Yeung J, et al. Potential therapeutic targets for lung repair during human ex vivo lung perfusion. Eur Respir J. 2020;55(4). doi:10.1183/13993003.02222-2019
   Web of Science ®Google Scholar
• Kang CH, Anraku M, Cypel M, et al. Transcriptional signatures in donor lungs from donation after cardiac death vs after brain death: a functional pathway analysis. J Heart Lung Transplant. 2011;30(3):289–298. doi:10.1016/j.healun.2010.09.004
   PubMed Web of Science ®Google Scholar
• Barrett T, Wilhite SE, Ledoux P, et al. NCBI GEO: archive for functional genomics data sets--update. Nucleic Acids Res. 2013;41(Databaseissue):D991–D995. doi:10.1093/nar/gks1193
   PubMed Web of Science ®Google Scholar
• Ritchie ME, Phipson B, Wu D, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47. doi:10.1093/nar/gkv007
   PubMed Web of Science ®Google Scholar
• Leek JT, Johnson WE, Parker HS, Jaffe AE, Storey JD. The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics. 2012;28(6):882–883. doi:10.1093/bioinformatics/bts034
   PubMed Web of Science ®Google Scholar
• Yu G, Wang LG, Han Y, He QY. clusterProfiler: an R package for comparing biological themes among gene clusters. Omics. 2012;16(5):284–287. doi:10.1089/omi.2011.0118
   PubMed Web of Science ®Google Scholar
• Newman AM, Liu CL, Green MR, et al. Robust enumeration of cell subsets from tissue expression profiles. Nature Methods. 2015;12(5):453–457. doi:10.1038/nmeth.3337
   PubMed Web of Science ®Google Scholar
• Hu K. Become competent within one day in generating boxplots and violin plots for a novice without prior R experience. Meth Protocols. 2020;3(4). doi:10.3390/mps3040064
   Google Scholar
• Szklarczyk D, Gable AL, Lyon D, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019;47(D1):D607–D613. doi:10.1093/nar/gky1131
   PubMed Web of Science ®Google Scholar
• Yang C, Delcher C, Shenkman E, Ranka S. Machine learning approaches for predicting high cost high need patient expenditures in health care. Biomed Eng Online. 2018;17(Suppl 1):131. doi:10.1186/s12938-018-0568-3
   PubMedGoogle Scholar
• Ellis K, Kerr J, Godbole S, Lanckriet G, Wing D, Marshall S. A random forest classifier for the prediction of energy expenditure and type of physical activity from wrist and Hip accelerometers. Physiol Meas. 2014;35(11):2191–2203. doi:10.1088/0967-3334/35/11/2191
   PubMed Web of Science ®Google Scholar
• Blanco JL, Porto-Pazos AB, Pazos A, Fernandez-Lozano C. Prediction of high anti-angiogenic activity peptides in silico using a generalized linear model and feature selection. Sci Rep. 2018;8(1):15688. doi:10.1038/s41598-018-33911-z
   PubMedGoogle Scholar
• Alderden J, Pepper GA, Wilson A, et al. Predicting pressure injury in critical care patients: a machine-learning model. Am J Crit Care. 2018;27(6):461–468. doi:10.4037/ajcc2018525
   PubMed Web of Science ®Google Scholar
• Wu J, Zhang F, Zheng X, et al. Identification of renal ischemia reperfusion injury subtypes and predictive strategies for delayed graft function and graft survival based on neutrophil extracellular trap-related genes. Front Immunol. 2022;13(1047367). doi:10.3389/fimmu.2022.1047367
   Google Scholar
• Robin X, Turck N, Hainard A, et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinf. 2011;12(77). doi:10.1186/1471-2105-12-77
   PubMedGoogle Scholar
• Snell GI, Yusen RD, Weill D, et al. Report of the ISHLT Working Group on Primary Lung Graft Dysfunction, part I: definition and grading-A 2016 Consensus Group statement of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2017;36(10):1097–1103. doi:10.1016/j.healun.2017.07.021
   PubMed Web of Science ®Google Scholar
• Van Raemdonck D, Hartwig MG, Hertz MI, et al. Report of the ISHLT Working Group on primary lung graft dysfunction Part IV: prevention and treatment: a 2016 Consensus Group statement of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2017;36(10):1121–1136. doi:10.1016/j.healun.2017.07.013
   PubMed Web of Science ®Google Scholar
• Merza M, Hartman H, Rahman M, et al. Neutrophil extracellular traps induce trypsin activation, inflammation, and tissue damage in mice with severe acute pancreatitis. Gastroenterology. 2015;149(7):1920–1931.e1928. doi:10.1053/j.gastro.2015.08.026
   PubMed Web of Science ®Google Scholar
• Lindstedt S, Niroomand A, Mittendorfer M, et al. Nothing but NETs: cytokine adsorption correlates with lower circulating nucleosomes and is associated with decreased primary graft dysfunction. J Heart Lung Transplant. 2023. doi:10.1016/j.healun.2023.06.011
   Web of Science ®Google Scholar
• Hakkim A, Fürnrohr BG, Amann K, et al. Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis. Proc Natl Acad Sci USA. 2010;107(21):9813–9818. doi:10.1073/pnas.0909927107
   PubMed Web of Science ®Google Scholar
• Scozzi D, Wang X, Liao F, et al. Neutrophil extracellular trap fragments stimulate innate immune responses that prevent lung transplant tolerance. Am J Transplant. 2019;19(4):1011–1023. doi:10.1111/ajt.15163
   PubMed Web of Science ®Google Scholar
• Parker C, Waters R, Leighton C, et al. Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomised trial. Lancet. 2010;376(9757):2009–2017. doi:10.1016/S0140-6736(10)62002-8
   PubMed Web of Science ®Google Scholar
• Pathania AS, Joshi A, Kumar S, et al. Reversal of boswellic acid analog BA145 induced caspase dependent apoptosis by PI3K inhibitor LY294002 and MEK inhibitor PD98059. Apoptosis. 2013;18(12):1561–1573. doi:10.1007/s10495-013-0889-4
   PubMed Web of Science ®Google Scholar
• Dhanalakshmi S, Agarwal C, Singh RP, Agarwal R. Silibinin up-regulates DNA-protein kinase-dependent p53 activation to enhance UVB-induced apoptosis in mouse epithelial JB6 cells. J Biol Chem. 2005;280(21):20375–20383.
   PubMed Web of Science ®Google Scholar
• Patil S, Lis LG, Schumacher RJ, et al. Phosphonooxymethyl prodrug of triptolide: synthesis, physicochemical characterization, and efficacy in human colon adenocarcinoma and ovarian cancer xenografts. J Med Chem. 2015;58(23):9334–9344. doi:10.1021/acs.jmedchem.5b01329
   PubMed Web of Science ®Google Scholar
• Bollag G, Hirth P, Tsai J, et al. Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature. 2010;467(7315):596–599. doi:10.1038/nature09454
   PubMed Web of Science ®Google Scholar
• Eder SK, Schwentner R, Ben Soussia P, et al. Vemurafenib acts as a molecular on-off switch governing systemic inflammation in Langerhans cell histiocytosis. Blood Adv. 2022;6(3):970–975. doi:10.1182/bloodadvances.2021005442
   PubMed Web of Science ®Google Scholar
• den Hengst WA, Gielis JF, Lin JY, Van Schil PE, De Windt LJ, Moens AL. Lung ischemia-reperfusion injury: a molecular and clinical view on a complex pathophysiological process. Am j Physiol Heart Circulatory Physiol. 2010;299(5):H1283–H1299. doi:10.1152/ajpheart.00251.2010
   PubMed Web of Science ®Google Scholar
• Herr AB, Ballister ER, Bjorkman PJ. Insights into IgA-mediated immune responses from the crystal structures of human FcalphaRI and its complex with IgA1-Fc. Nature. 2003;423(6940):614–620. doi:10.1038/nature01685
   PubMed Web of Science ®Google Scholar
• Aleyd E, van Hout MW, Ganzevles SH, et al. IgA enhances NETosis and release of neutrophil extracellular traps by polymorphonuclear cells via Fcα receptor I. J Immunol. 2014;192(5):2374–2383. doi:10.4049/jimmunol.1300261
   PubMed Web of Science ®Google Scholar
• Wehrli M, Cortinas-Elizondo F, Hlushchuk R, et al. Human IgA Fc receptor FcαRI (CD89) triggers different forms of neutrophil death depending on the inflammatory microenvironment. J Immunol. 2014;193(11):5649–5659. doi:10.4049/jimmunol.1400028
   PubMed Web of Science ®Google Scholar
• Vogl T, Pröpper C, Hartmann M, et al. S100A12 is expressed exclusively by granulocytes and acts independently from MRP8 and MRP14. J Biol Chem. 1999;274(36):25291–25296. doi:10.1074/jbc.274.36.25291
   PubMed Web of Science ®Google Scholar
• Pietzsch J, Hoppmann S. Human S100A12: a novel key player in inflammation? Amino Acids. 2009;36(3):381–389. doi:10.1007/s00726-008-0097-7
   PubMed Web of Science ®Google Scholar
• Jiang X, Huang CM, Feng CM, Xu Z, Fu L, Wang XM. Associations of serum S100A12 with severity and prognosis in patients with community-acquired pneumonia: a prospective cohort study. Front Immunol. 2021;12(714026). doi:10.3389/fimmu.2021.714026
   Google Scholar
• Li Y, He Y, Chen S, et al. S100A12 as biomarker of disease severity and prognosis in patients with idiopathic pulmonary fibrosis. Front Immunol. 2022;13(810338). doi:10.3389/fimmu.2022.810338
   Google Scholar
• Amini H, Knepp B, Rodriguez F, et al. Early peripheral blood gene expression associated with good and poor 90-day ischemic stroke outcomes. J Neuroinflammation. 2023;20(1):13. doi:10.1186/s12974-022-02680-y
   PubMed Web of Science ®Google Scholar
• Wakisaka Y, Ago T, Kamouchi M, et al. Plasma S100A12 is associated with functional outcome after ischemic stroke: research for biomarkers in ischemic stroke. J Neurol Sci. 2014;340(1–2):75–79. doi:10.1016/j.jns.2014.02.031
   PubMed Web of Science ®Google Scholar
• Lei H. A two-gene marker for the two-tiered innate immune response in COVID-19 patients. PLoS One. 2023;18(1):e0280392. doi:10.1371/journal.pone.0280392
   PubMed Web of Science ®Google Scholar
• Foell D, Wittkowski H, Kessel C, et al. Proinflammatory S100A12 can activate human monocytes via Toll-like receptor 4. Am J Respir Crit Care Med. 2013;187(12):1324–1334. doi:10.1164/rccm.201209-1602OC
   PubMed Web of Science ®Google Scholar
• Ingels C, Derese I, Wouters PJ, Van den Berghe G, Vanhorebeek I. Soluble RAGE and the RAGE ligands HMGB1 and S100A12 in critical illness: impact of glycemic control with insulin and relation with clinical outcome. Shock. 2015;43(2):109–116. doi:10.1097/shk.0000000000000278
   PubMed Web of Science ®Google Scholar
• Zhang Z, Han N, Shen Y. S100A12 promotes inflammation and cell apoptosis in sepsis-induced ARDS via activation of NLRP3 inflammasome signaling. Mol Immunol. 2020;122:38–48. doi:10.1016/j.molimm.2020.03.022
   PubMed Web of Science ®Google Scholar
• Zhang X, Shen R, Shu Z, Zhang Q, Chen Z. S100A12 promotes inflammation and apoptosis in ischemia/reperfusion injury via ERK signaling in vitro study using PC12 cells. Pathol Int. 2020;70(7):403–412. doi:10.1111/pin.12924
   PubMed Web of Science ®Google Scholar
• Hübner RH, Meffert S, Mundt U, et al. Matrix metalloproteinase-9 in bronchiolitis obliterans syndrome after lung transplantation. Eur Respir J. 2005;25(3):494–501. doi:10.1183/09031936.05.00091804
   PubMed Web of Science ®Google Scholar
• Gomez DE, Alonso DF, Yoshiji H, Thorgeirsson UP. Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. Eur J Cell Biol. 1997;74(2):111–122.
   PubMed Web of Science ®Google Scholar
• Yano M, Omoto Y, Yamakawa Y, et al. Increased matrix metalloproteinase 9 activity and mRNA expression in lung ischemia-reperfusion injury. J Heart Lung Transplant. 2001;20(6):679–686. doi:10.1016/s1053-2498(01)00250-9
   PubMed Web of Science ®Google Scholar
• Zhou P, Song NC, Zheng ZK, Li YQ, Li JS. MMP2 and MMP9 contribute to lung ischemia-reperfusion injury via promoting pyroptosis in mice. BMC Pulm Med. 2022;22(1):230. doi:10.1186/s12890-022-02018-7
   PubMed Web of Science ®Google Scholar
• Wang Y, Li M, Stadler S, et al. Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation. J Cell Biol. 2009;184(2):205–213. doi:10.1083/jcb.200806072
   PubMed Web of Science ®Google Scholar
• Papayannopoulos V, Metzler KD, Hakkim A, Zychlinsky A. Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps. J Cell Biol. 2010;191(3):677–691. doi:10.1083/jcb.201006052
   PubMed Web of Science ®Google Scholar
• Thiam HR, Wong SL, Qiu R, 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(13):7326–7337. doi:10.1073/pnas.1909546117
   PubMed Web of Science ®Google Scholar
• Suzuki M, Ikari J, Anazawa R, et al. PAD4 deficiency improves bleomycin-induced neutrophil extracellular traps and fibrosis in mouse lung. Am J Respir Cell Mol Biol. 2020;63(6):806–818. doi:10.1165/rcmb.2019-0433OC
   PubMed Web of Science ®Google Scholar
• Biron BM, Chung CS, Chen Y, 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(5):1817–1828. doi:10.4049/jimmunol.1700639
   PubMed Web of Science ®Google Scholar