Crosstalk between neutrophil extracellular traps and immune regulation: insights into pathobiology and therapeutic implications of transfusion-related acute lung injury
Yi Liu, Rong Wang, Congkuan Song, Song Ding, Yifan Zuo, Ke Yi, Ning Li, Bo Wang, Qing Geng
Frontiers in Immunology, doi:10.3389/fimmu.2023.1324021
Transfusion-related acute lung injury (TRALI) is the leading cause of transfusionassociated death, occurring during or within 6 hours after transfusion. Reports indicate that TRALI can be categorized as having or lacking acute respiratory distress syndrome (ARDS) risk factors. There are two types of TRALI in terms of its pathogenesis: antibody-mediated and non-antibody-mediated. The key initiation steps involve the priming and activation of neutrophils, with neutrophil extracellular traps (NETs) being established as effector molecules formed by activated neutrophils in response to various stimuli. These NETs contribute to the production and release of reactive oxygen species (ROS) and participate in the destruction of pulmonary vascular endothelial cells. The significant role of NETs in TRALI is well recognized, offering a potential pathway for TRALI treatment. Moreover, platelets, macrophages, endothelial cells, and complements have been identified as promoters of NET formation. Concurrently, studies have demonstrated that the storage of platelets and concentrated red blood cells (RBC) can induce TRALI through bioactive lipids. In this article, recent clinical and pre-clinical studies on the pathophysiology and pathogenesis of TRALI are reviewed to further illuminate the mechanism through which NETs induce TRALI. This review aims to propose new therapeutic strategies for TRALI, with the hope of effectively improving its poor prognosis.
Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Appendix The proteins/genes described in this review.
References
Adrover, Carrau, Daßler-Plenker, Bram, Chandar et al., Disulfiram inhibits neutrophil extracellular trap formation and protects rodents from acute lung injury and SARS-CoV-2 infection, JCI Insight,
doi:10.1172/jci.insight.157342Alfaro, Teijeira, Onate, Perez, Sanmamed et al., Tumor-produced interleukin-8 attracts human myeloid-derived suppressor cells and elicits extrusion of neutrophil extracellular traps (NETs), Clin Cancer Res,
doi:10.1158/1078-0432.CCR-15-2463Amara, Cooper, Voronkova, Webb, Lynch et al., Selective activation of PFKL suppresses the phagocytic oxidative burst, Cell,
doi:10.1016/j.cell.2021.07.004Apel, Andreeva, Knackstedt, Streeck, Frese et al., The cytosolic DNA sensor cGAS recognizes neutrophil extracellular traps, Sci Signal,
doi:10.1126/scisignal.aax7942Awasthi, Nagarkoti, Sadaf, Chandra, Kumar et al., Glycolysis dependent lactate formation in neutrophils: A metabolic link between NOX-dependent and independent NETosis, Biochim Biophys Acta Mol Basis Dis,
doi:10.1016/j.bbadis.2019.165542Azevedo, Rochael, Guimaraes-Costa, De Souza-Vieira, Ganilho et al., A metabolic shift toward pentose phosphate pathway is necessary for amyloid fibriland phorbol 12-myristate 13-acetate-induced neutrophil extracellular trap (NET) formation, J Biol Chem,
doi:10.1074/jbc.M115.640094Baudel, Vigneron, Pras-Landre, Joffre, Marjot et al., Transfusion-related acute lung injury (TRALI) after intravenous immunoglobulins: French multicentre study and literature review, Clin Rheumatol,
doi:10.1007/s10067-019-04832-7Bertini, Allegretti, Bizzarri, Moriconi, Locati et al., Noncompetitive allosteric inhibitors of the inflammatory chemokine receptors CXCR1 and CXCR2: prevention of reperfusion injury, Proc Natl Acad Sci,
doi:10.1084/jem.20181102Borella, Biasi, Paolini, Boraldi, Tartaro et al., Metabolic reprograming shapes neutrophil functions in severe COVID-19, Eur J Immunol,
doi:10.1002/eji.202149481Brinkmann, Reichard, Goosmann, Fauler, Uhlemann et al., Neutrophil extracellular traps kill bacteria, Science,
doi:10.1126/science.1092385Britt, Lika, Giese, Schoen, Seim et al., Switching to the cyclic pentose phosphate pathway powers the oxidative burst in activated neutrophils, Nat Metab,
doi:10.1038/s42255-022-00550-8Cao, Zhang, Wang, Yang, Ma et al., Inhibition of the glycolytic activator PFKFB3 in endothelium induces tumor vessel normalization, impairs metastasis, and improves chemotherapy, Proc Natl Acad Sci,
doi:10.1016/j.ccell.2016.10.006Caudrillier, Kessenbrock, Gilliss, Nguyen, Marques et al., Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury, J Clin Invest,
doi:10.1172/JCI61303Chapman, Lyon, Simpson, Mason, Beynon et al., Caught in a trap? Proteomic analysis of neutrophil extracellular traps in rheumatoid arthritis and systemic lupus erythematosus, Front Immunol,
doi:10.3389/fimmu.2019.00423Chauhan, Demon, Walle, Paerewijck, Zecchin et al., GSDMD drives canonical inflammasome-induced neutrophil pyroptosis and is dispensable for NETosis, EMBO Rep,
doi:10.15252/embr.202154277Chen, Gross, Sotomayor, Stacey, Tschopp et al., The neutrophil NLRC4 inflammasome selectively promotes IL-1beta maturation without pyroptosis during acute Salmonella challenge, Cell Rep,
doi:10.1016/j.celrep.2014.06.028Chen, Monteleone, Boucher, Sollberger, Ramnath et al., Noncanonical inflammasome signaling elicits gasdermin D-dependent neutrophil extracellular traps, Sci Immunol,
doi:10.1126/sciimmunol.aar6676Chen, Zhao, Lai, Zhang, Yang et al., Neutrophil extracellular traps promote macrophage pyroptosis in sepsis, Cell Death Dis,
doi:10.1038/s41419-017-0090-8Cieloch, Kuzmicka, Mroczek, Stelmaszczyk-Emmel, Demkow, Secretomes of M1 and M2 macrophages decrease the release of neutrophil extracellular traps, Sci Rep,
doi:10.1038/s41598-023-42167-1Cleary, Kwaan, Tian, Calabrese, Mallavia et al., C5aR1 signaling triggers lung immunopathology in COVID-19 through neutrophil extracellular traps, J Clin Invest,
doi:10.1172/JCI163105Cui, Yang, Tao, Peng, Luo et al., Neutrophil extracellular traps induce alveolar macrophage pyroptosis by regulating NLRP3 deubiquitination, aggravating the development of septic lung injury, J Inflamm Res,
doi:10.2147/JIR.S366436Domer, Walther, Moller, Behnen, Laskay, Neutrophil extracellular traps activate proinflammatory functions of human neutrophils, Front Immunol,
doi:10.3389/fimmu.2021.636954Doring, Libby, Soehnlein, Neutrophil extracellular traps participate in cardiovascular diseases: recent experimental and clinical insights, Circ Res,
doi:10.1161/CIRCRESAHA.120.315931Douda, Khan, Grasemann, Palaniyar, SK3 channel and mitochondrial ROS mediate NADPH oxidase-independent NETosis induced by calcium influx, Proc Natl Acad Sci,
doi:10.1073/pnas.1414055112Folco, Mawson, Vromman, Bernardes-Souza, Franck et al., Neutrophil extracellular traps induce endothelial cell activation and tissue factor production through interleukin-1alpha and cathepsin G, Arterioscler Thromb Vasc Biol,
doi:10.1161/ATVBAHA.118.311150Ghergurovich, Garcia-Canaveras, Wang, Schmidt, Zhang et al., A small molecule G6PD inhibitor reveals immune dependence on pentose phosphate pathway, Nat Chem Biol,
doi:10.1038/s41589-020-0533-xGoldspink, Schmitz, Babyak, Brauns, Milleck et al., Kidney medullary sodium chloride concentrations induce neutrophil and monocyte extracellular DNA traps that defend against pyelonephritis, vivo Kidney Int,
doi:10.1016/j.kint.2023.03.034Gomes, Varady, Lourenco, Mizurini, Rondon et al., IL-1beta blockade attenuates thrombosis in a neutrophil extracellular trap-dependent breast cancer model, Front Immunol,
doi:10.3389/fimmu.2019.02088Gregoire, Uhel, Lesouhaitier, Gacouin, Guirriec et al., Impaired efferocytosis and neutrophil extracellular trap clearance by macrophages in ARDS, Eur Respir J,
doi:10.1183/13993003.02590-2017Haider, Kral-Pointner, Mayer, Richter, Kaun et al., Neutrophil extracellular trap degradation by differently polarized macrophage subsets, Arterioscler Thromb Vasc Biol,
doi:10.1161/ATVBAHA.120.314883Herre, Cedervall, Mackman, Olsson, Neutrophil extracellular traps in the pathology of cancer and other inflammatory diseases, Physiol Rev,
doi:10.1152/physrev.00062.2021Hu, Liu, Xia, Zhang, Zhang et al., FDA-approved disulfiram inhibits pyroptosis by blocking gasdermin D pore formation, Nat Immunol,
doi:10.1038/s41590-020-0669-6Humphries, Shmuel-Galia, Ketelut-Carneiro, Li, Wang et al., Necrostatin-1 alleviates diffuse pulmonary haemorrhage by preventing the release of NETs via inhibiting NE/ GSDMD activation in murine lupus, Front Immunol,
doi:10.1155/2023/4743975Jaillon, Peri, Delneste, Fremaux, Doni et al., The humoral pattern recognition receptor PTX3 is stored in neutrophil granules and localizes in extracellular traps, J Exp Med,
doi:10.1084/jem.20061301Jayne, Merkel, Schall, Bekker, Group, Avacopan for the treatment of ANCA-associated vasculitis, N Engl J Med,
doi:10.1056/NEJMoa2023386Jiao, Zhang, Liu, Zhou, Qi et al., Exosomal PGE2 from M2 macrophages inhibits neutrophil recruitment and NET formation through lipid mediator class switching in sepsis, J BioMed Sci,
doi:10.1186/s12929-023-00957-9Kambara, Liu, Zhang, Liu, Bajrami et al., Gasdermin D exerts anti-inflammatory effects by promoting neutrophil death, Cell Rep,
doi:10.1016/j.celrep.2018.02.067Kapur, Kasetty, Rebetz, Egesten, Semple et al., Osteopontin mediates murine transfusion-related acute lung injury via stimulation of pulmonary neutrophil accumulation, Nature,
doi:10.1038/s41586-022-04802-1Karmakar, Minns, Greenberg, Diaz-Aponte, Pestonjamasp et al., N-GSDMD trafficking to neutrophil organelles facilitates IL-1beta release independently of plasma membrane pores and pyroptosis, Nat Commun,
doi:10.1038/s41467-020-16043-9Kim, Jang, Dharaneeswaran, Li, Bhide et al., Endothelial pyruvate kinase M2 maintains vascular integrity, J Clin Invest,
doi:10.1172/JCI120912Kono, Saigo, Takagi, Kawauchi, Wada et al., Morphological and flow-cytometric analysis of haemin-induced human neutrophil activation: implications for transfusion-related acute lung injury, Blood Transfus,
doi:10.2450/2012.0141-11Kono, Saigo, Takagi, Takahashi, Kawauchi et al., Hemerelated molecules induce rapid production of neutrophil extracellular traps, Transfusion,
doi:10.1111/trf.12700Kovacs, Oh, Maltez, Mcglaughon, Verma et al., Neutrophil caspase-11 is essential to defend against a cytosol-invasive bacterium, Cell Rep,
doi:10.1016/j.celrep.2020.107967Lande, Ganguly, Facchinetti, Frasca, Conrad et al., Neutrophils activate plasmacytoid dendritic cells by releasing self-DNA-peptide complexes in systemic lupus erythematosus, Sci Transl Med,
doi:10.1126/scitranslmed.3001180Lande, Gregorio, Facchinetti, Chatterjee, Wang et al., Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide, Nature,
doi:10.1038/nature06116Lauth, Kockritz-Blickwede, Mcnamara, Myskowski, Zinkernagel et al., M1 protein allows Group A streptococcal survival in phagocyte extracellular traps through cathelicidin inhibition, J Innate Immun,
doi:10.1159/000203645Lazzaretto, Fadeel, Intra-and extracellular degradation of neutrophil extracellular traps by macrophages and dendritic cells, J Immunol,
doi:10.4049/jimmunol.1800159Le, Wu, Liu, Wu, Hu et al., MiR-144-induced KLF2 inhibition and NF-kappaB/CXCR1 activation promote neutrophil extracellular trap-induced transfusion-related acute lung injury, J Cell Mol Med,
doi:10.1111/jcmm.16650Leffler, Martin, Gullstrand, Tyden, Lood et al., Neutrophil extracellular traps that are not degraded in systemic lupus erythematosus activate complement exacerbating the disease, J Immunol,
doi:10.4049/jimmunol.1102404Leppkes, Knopf, Naschberger, Lindemann, Singh et al., Vascular occlusion by neutrophil extracellular traps in COVID-19, EBioMedicine,
doi:10.1016/j.ebiom.2020.102925Li, Hook, Ding, Chung, Mettlen, Neutrophil metabolomics in severe COVID-19 reveal GAPDH as a suppressor of neutrophil extracellular trap formation, Nat Commun,
doi:10.1038/s41467-023-37567-wLi, Wang, Liu, Li, Zhang et al., Neutrophil extracellular traps induce intestinal damage and thrombotic tendency in inflammatory bowel disease, J Crohns Colitis,
doi:10.1093/ecco-jcc/jjz132Lin, Hu, Hu, Li, Wang et al., NET-triggered NLRP3 activation and IL18 release drive oxaliplatin-induced peripheral neuropathy, Cancer Immunol Res,
doi:10.1158/2326-6066.CIR-22-0197Liu, Xiao, Zhou, Wang, Peng et al., PFKFB3 promotes sepsisinduced acute lung injury by enhancing NET formation by CXCR4(hi) neutrophils, Int Immunopharmacol,
doi:10.1016/j.intimp.2023.110737Liu, Yang, Gao, Yu, Shi et al., NLRP3 activation induced by neutrophil extracellular traps sustains inflammatory response in the diabetic wound, Clin Sci (Lond),
doi:10.1042/CS20180600Lood, Blanco, Purmalek, Carmona-Rivera, Ravin et al., Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease, Nat Med,
doi:10.1038/nm.4027Luo, Dai, Feng, Ding, Shao et al., Suppression of lncRNA NLRP3 inhibits NLRP3-triggered inflammatory responses in early acute lung injury, Cell Death Dis,
doi:10.1038/s41419-021-04180-yMcdonald, Davis, Kim, Tse, Esmon et al., Platelets and neutrophil extracellular traps collaborate to promote intravascular coagulation during sepsis in mice, Blood,
doi:10.1182/blood-2016-09-741298Metzler, Goosmann, Lubojemska, Zychlinsky, Papayannopoulos, A myeloperoxidase-containing complex regulates neutrophil elastase release and actin dynamics during NETosis, Cell Rep,
doi:10.1016/j.celrep.2014.06.044Mistry, Nakabo, Neil, Goel, Jiang et al., Transcriptomic, epigenetic, and functional analyses implicate neutrophil diversity in the pathogenesis of systemic lupus erythematosus, Proc Natl Acad Sci,
doi:10.1073/pnas.1908576116Munzer, Negro, Fukui, Di Meglio, Aymonnier et al., NLRP3 inflammasome assembly in neutrophils is supported by PAD4 and promotes NETosis under sterile conditions, Front Immunol,
doi:10.3389/fimmu.2021.683803Peters, Van Hezel, Cortjens, Boer, Van Bruggen et al., Transfusion of 35-day stored RBCs in the presence of endotoxemia does not result in lung injury in humans, Crit Care Med,
doi:10.1097/CCM.0000000000001614Peters, Van Stein, Vlaar, Antibody-mediated transfusion-related acute lung injury; from discovery to prevention, Br J Haematol,
doi:10.1111/bjh.13459Peters, Vervaart, Van Bruggen, De Korte, Nieuwland et al., Non-polar lipids accumulate during storage of transfusion products and do not 12, Immunity,
doi:10.1016/j.immuni.2021.06.006Pilsczek, Salina, Poon, Fahey, Yipp et al., A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus, J Immunol,
doi:10.4049/jimmunol.1000675Rathkey, Zhao, Liu, Chen, Yang et al., Chemical disruption of the pyroptotic pore-forming protein gasdermin D inhibits inflammatory cell death and sepsis, Sci Immunol,
doi:10.1126/sciimmunol.aat2738Rodriguez-Espinosa, Rojas-Espinosa, Moreno-Altamirano, Lopez-Villegas, Sanchez-Garcia, Metabolic requirements for neutrophil extracellular traps formation, Immunology,
doi:10.1111/imm.12437Sadiku, Willson, Dickinson, Murphy, Harris et al., Prolyl hydroxylase 2 inactivation enhances glycogen storage and promotes excessive neutrophilic responses, J Clin Invest,
doi:10.1172/JCI90848Sano, Maejima, Nakagama, Shiheido-Watanabe, Tamura et al., Neutrophil extracellular traps-mediated Beclin-1 suppression aggravates atherosclerosis by inhibiting macrophage autophagy, Front Cell Dev Biol,
doi:10.3389/fcell.2022.876147Santoni, Pericat, Gorse, Buyck, Pinilla et al., Caspase-1driven neutrophil pyroptosis and its role in host susceptibility to Pseudomonas aeruginosa, PloS Pathog,
doi:10.1371/journal.ppat.1010305Schauer, Janko, Munoz, Zhao, Kienhofer et al., Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines, Nat Med,
doi:10.1038/nm.3547Schmickl, Mastrobuoni, Filippidis, Shah, Radic et al., Male-predominant plasma transfusion strategy for preventing transfusion-related acute lung injury: a systematic review, Crit Care Med,
doi:10.1097/CCM.0000000000000675Schneider, Machado, Veras, Maganin, De Souza et al., Neutrophil extracellular traps mediate joint hyperalgesia induced by immune inflammation, Rheumatol,
doi:10.1093/rheumatology/keaa794Schnitzler, Hoogeveen, Ali, Prange, Waissi et al., Atherogenic lipoprotein(a) increases vascular glycolysis, thereby facilitating inflammation and leukocyte extravasation, Circ Res,
doi:10.1161/CIRCRESAHA.119.316206Shi, Liu, Cao, Ma, Zhu et al., Inhibition of neutrophil extracellular trap formation ameliorates neuroinflammation and neuronal apoptosis via STING-dependent IRE1alpha/ASK1/JNK signaling pathway in mice with traumatic brain injury, J Neuroinflamm,
doi:10.1186/s12974-023-02903-wShi, Zhao, Wang, Shi, Wang et al., Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death, Nature,
doi:10.1038/nature15514Silliman, Kelher, Khan, Lasarre, West et al., Experimental prestorage filtration removes antibodies and decreases lipids in RBC supernatants mitigating TRALI in vivo, Blood,
doi:10.1182/blood-2013-10-532424Silva, Wanderley, Veras, Sonego, Nascimento et al., Gasdermin D inhibition prevents multiple organ dysfunction during sepsis by blocking NET formation, Crit Care,
doi:10.1186/s13054-022-04062-5Skov, Beurskens, Zachariae, Reitamo, Teeling et al., IL-8 as antibody therapeutic target in inflammatory diseases: reduction of clinical activity in palmoplantar pustulosis, J Immunol,
doi:10.4049/jimmunol.181.1.669Sollberger, Choidas, Burn, Habenberger, Lucrezia et al., Gasdermin D plays a vital role in the generation of neutrophil extracellular traps, Sci Immunol,
doi:10.1126/sciimmunol.aar6689Stojkov, Claus, Kozlowski, Oberson, Scharen et al., NET formation is independent of gasdermin D and pyroptotic cell death, Sci Signal,
doi:10.1126/scisignal.abm0517Suksawad, Udompornpitak, Thawinpipat, Korwattanamongkol, Visitchanakun et al., Cyclic GMP-AMP synthase (cGAS) deletion reduces severity in bilateral nephrectomy mice through changes in neutrophil extracellular traps and mitochondrial respiration, Biomedicines,
doi:10.3390/biomedicines11041208Swiecki, Colonna, The multifaceted biology of plasmacytoid dendritic cells, Nat Rev Immunol,
doi:10.1038/nri3865Teijeira, Garasa, Gato, Alfaro, Migueliz et al., CXCR1 and CXCR2 chemokine receptor agonists produced by tumors induce neutrophil extracellular traps that interfere with immune cytotoxicity, Immunity,
doi:10.1016/j.immuni.2020.03.001Thomas, Carbo, Curtis, Martinod, Mazo et al., Extracellular DNA traps are associated with the pathogenesis of TRALI in humans and mice, Blood,
doi:10.1182/blood-2012-01-405183Torres Caban, Yang, Lai, Yang, Subach et al., Tuning the sensitivity of genetically encoded fluorescent potassium indicators through structure-guided and genome mining strategies, ACS Sens,
doi:10.1021/acssensors.1c02201Urban, Ermert, Schmid, Abu-Abed, Goosmann et al., Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans, PLoS Pathog,
doi:10.1371/journal.ppat.1000639Van Der Velden, Van Osch, Seghier, Bentlage, Mok et al., Complement C5a induces the generation of neutrophil extracellular traps by inhibiting mitochondrial STAT3 to promote the development of arterial thrombosis, Thromb J,
doi:10.1186/s12959-022-00384-0Van Hezel, Boshuizen, Peters, Straat, Vlaar et al., Red blood cell transfusion results in adhesion of neutrophils in human endotoxemia and in critically ill patients with sepsis, Transfusion,
doi:10.1111/trf.15613Van Raam, Sluiter, De Wit, Roos, Verhoeven et al., Mitochondrial membrane potential in human neutrophils is maintained by complex III activity in the absence of supercomplex organisation, PLoS One,
doi:10.1371/journal.pone.0002013Vlaar, Toy, Fung, Looney, Juffermans et al., A consensus redefinition of transfusion-related acute lung injury, Transfusion,
doi:10.1111/trf.15311Wang, Cao, Gorshkov, Zhou, Yang et al., Ablation of endothelial Pfkfb3 protects mice from acute lung injury in LPS-induced endotoxemia, Pharmacol Res,
doi:10.1016/j.phrs.2019.104292Wang, Li, Chen, Yuan, Su et al., GSDMD-dependent neutrophil extracellular traps promote macrophage-to-myofibroblast transition and renal fibrosis in obstructive nephropathy, Cell Death Dis,
doi:10.1038/s41419-022-05138-4Wang, Li, Stadler, Correll, Li et al., Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation, J Cell Biol,
doi:10.1083/jcb.200806072Wang, Wang, Zhao, Chen, Pluthero et al., NETosing neutrophils activate complement both on their own NETs and bacteria via alternative and non-alternative pathways, Clin Exp Immunol,
doi:10.1159/000356980Wang, Wu, Yan, Wang, Wu, M1-polarized alveolar macrophages are crucial in a mouse model of transfusion-related acute lung injury, Transfusion,
doi:10.1111/trf.15609Warnatsch, Ioannou, Wang, Papayannopoulos, Inflammation. Neutrophil extracellular traps license macrophages for cytokine production in atherosclerosis, Science,
doi:10.1126/science.aaa8064Wei, Zou, Xie, Wang, Huang et al., EDIL3 deficiency ameliorates adverse cardiac remodelling by neutrophil extracellular traps (NET)mediated macrophage polarization, Cardiovasc Res,
doi:10.1093/cvr/cvab269Wigerblad, Kaplan, Neutrophil extracellular traps in systemic autoimmune and autoinflammatory diseases, Nat Rev Immunol,
doi:10.1038/s41577-022-00787-0Wu, Huang, Hamanaka, Krause, Oh et al., HIF-1alpha is required for disturbed flow-induced metabolic reprogramming in human and porcine vascular endothelium, Elife,
doi:10.7554/eLife.25217Xie, Yang, Zhu, Gao, Jiang et al., Microparticles in red cell concentrates prime polymorphonuclear neutrophils and cause acute lung injury in a two-event mouse model, Int Immunopharmacol,
doi:10.1016/j.intimp.2017.11.029Xie, Zhu, Wan, Zhao, Meng et al., GSDMD-mediated NETosis promotes the development of acute respiratory distress syndrome, Eur J Immunol,
doi:10.1002/eji.202250011Xu, Zhang, Pelayo, Monestier, Ammollo et al., Extracellular histones are major mediators of death in sepsis, Nat Med,
doi:10.1038/nm.2053Yalcinkaya, Fotakis, Liu, Endo-Umeda, Dou et al., Cholesterol accumulation in macrophages drives NETosis in atherosclerotic plaques via IL-1beta secretion, Cardiovasc Res,
doi:10.1093/cvr/cvac189Yang, Duan, Liu, Xiong, Guan et al., A COX-2/ sEH dual inhibitor PTUPB alleviates lipopolysaccharide-induced acute lung injury in mice by inhibiting NLRP3 inflammasome activation, Theranostics,
doi:10.7150/thno.43108Yang, Feng, Chen, Wang, Chen et al., Disulfiram accelerates diabetic foot ulcer healing by blocking NET formation via suppressing the NLRP3/ Caspase-1/GSDMD pathway, Transl Res,
doi:10.1016/j.trsl.2022.10.008Yipp, Petri, Salina, Jenne, Scott et al., Infectioninduced NETosis is a dynamic process involving neutrophil multitasking in vivo, Nat Med,
doi:10.1038/nm.2847Yousefi, Mihalache, Kozlowski, Schmid, Hu, Viable neutrophils release mitochondrial DNA to form neutrophil extracellular traps, Cell Death Differ,
doi:10.1038/cdd.2009.96Zhang, Xu, Xu, Ye, Drug repurposing of ivermectin abrogates neutrophil extracellular traps and prevents melanoma metastasis, Front Oncol,
doi:10.3389/fonc.2022.989167Zhao, Liang, Ye, Wu, Qin et al., GSDMD promotes neutrophil extracellular traps via mtDNA-cGAS-STING pathway during lung ischemia/reperfusion, Cell Death Discov,
doi:10.1038/s41420-023-01663-zZhao, Pan, Zhang, Ma, Zhang et al., Neutrophil extracellular traps in inflammatory bowel diseases: Implications in pathogenesis and therapeutic targets, Semin Cancer Biol,
doi:10.1038/ncomms7673Ziogas, Sajib, Lim, Alves, Das et al., PKM2 regulates endothelial cell junction dynamics and angiogenesis via ATP production, FASEB J,
doi:10.1038/s41598-019-50866-xZuber, Fakhouri, Roumenina, Loirat, Vfrench et al., for a HCG. Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies, Nat Rev Nephrol,
doi:10.1038/nrneph.2012.214
