PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps
Open accessAbstract
Neutrophils trap and kill bacteria by forming highly decondensed chromatin structures, termed neutrophil extracellular traps (NETs). We previously reported that histone hypercitrullination catalyzed by peptidylarginine deiminase 4 (PAD4) correlates with chromatin decondensation during NET formation. However, the role of PAD4 in NET-mediated bacterial trapping and killing has not been tested. Here, we use PAD4 knockout mice to show that PAD4 is essential for NET-mediated antibacterial function. Unlike PAD4+/+ neutrophils, PAD4−/− neutrophils cannot form NETs after stimulation with chemokines or incubation with bacteria, and are deficient in bacterial killing by NETs. In a mouse infectious disease model of necrotizing fasciitis, PAD4−/− mice are more susceptible to bacterial infection than PAD4+/+ mice due to a lack of NET formation. Moreover, we found that citrullination decreased the bacterial killing activity of histones and nucleosomes, which suggests that PAD4 mainly plays a role in chromatin decondensation to form NETs instead of increasing histone-mediated bacterial killing. Our results define a role for histone hypercitrullination in innate immunity during bacterial infection.
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PAD4 is the enzyme responsible for histone modifications required for decondensing neutrophil DNA before expulsion.
“Next, we determined the importance of peptidylarginine deiminase type 4 (PAD4), the enzyme responsible for histone modifications required for decondensing neutrophil DNA before expulsion (25).”
From Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps (2016) · cites this paper as [25]
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Chromatin modifications and their function
Kouzarides, T. (2007) · Cell · doi:10.1016/j.cell.2007.02.005 · Cited by 10,883 · see citing works
Neutrophil Extracellular Traps Kill Bacteria
Brinkmann, V., Reichard, U., Goosmann, C., Fauler, B., Uhlemann, Y., Weiss, D. S., Weinrauch, Y., & Zychlinsky, A. (2004) · Science · doi:10.1126/science.1092385 · Cited by 10,268 · see citing works
Jenuwein, T., & Allis, C. D. (2001) · Science · doi:10.1126/science.1063127 · Cited by 9,756 · see citing works
Novel cell death program leads to neutrophil extracellular traps
Fuchs, T. A., Abed, U., Goosmann, C., Hurwitz, R., Schulze, I., Wahn, V., Weinrauch, Y., Brinkmann, V., & Zychlinsky, A. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200606027 · Cited by 3,197 · see citing works
Neutrophils and immunity: challenges and opportunities
Nathan, C. (2006) · Nature reviews. Immunology · doi:10.1038/nri1785 · Cited by 2,971 · see citing works
Segal, A. W. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115653 · Cited by 1,783 · see citing works
Wang, Y., Li, M., Stadler, S. C., Correll, S., Li, P., Wang, D., Hayama, R., Leonelli, L., Han, H., Grigoryev, S. A., et al. (2009) · The Journal of Cell Biology · doi:10.1083/jcb.200806072 · Cited by 1,532 · see citing works
Self-citationSimplified mammalian DNA isolation procedure
Laird, P. W., Zijderveld, A., Linders, K., Rudnicki, M. A., Jaenisch, R., & Berns, A. J. M. (1991) · Nucleic Acids Research · doi:10.1093/nar/19.15.4293 · Cited by 1,497 · see citing works
The structure of DNA in the nucleosome core
Richmond, T. J., & Davey, C. A. (2003) · Nature · doi:10.1038/nature01595 · Cited by 1,287 · see citing works
Human PAD4 Regulates Histone Arginine Methylation Levels via Demethylimination
Wang, Y., Wysocka, J., Sayegh, J., Lee, Y., Perlin, J. R., Leonelli, L., Sonbuchner, L. S., McDonald, C. H., Cook, R. G., Dou, Y., et al. (2004) · Science · doi:10.1126/science.1101400 · Cited by 1,013 · see citing works
Self-citationBeneficial suicide: why neutrophils die to make NETs
Brinkmann, V., & Zychlinsky, A. (2007) · Nature Reviews Microbiology · doi:10.1038/nrmicro1710 · Cited by 937 · see citing works
Histone Deimination Antagonizes Arginine Methylation
Cuthbert, G. L., Daujat, S., Snowden, A. W., Erdjument‐Bromage, H., Hagiwara, T., Yamada, M., Schneider, R., Gregory, P. D., Tempst, P., Bannister, A. J., et al. (2004) · Cell · doi:10.1016/j.cell.2004.08.020 · Cited by 840 · see citing works
Buchanan, J. T., Simpson, A. J., Aziz, R. K., Liu, G. Y., Kristian, S. A., Kotb, M., Feramisco, J. R., & Nizet, V. (2006) · Current Biology · doi:10.1016/j.cub.2005.12.039 · Cited by 683 · see citing works
Restoration of NET formation by gene therapy in CGD controls aspergillosis
Bianchi, M., Hakkim, A., Brinkmann, V., Siler, U., Seger, R. A., Zychlinsky, A., & Reichenbach, J. (2009) · Blood · doi:10.1182/blood-2009-05-221606 · Cited by 593 · see citing works
Histone Deimination As a Response to Inflammatory Stimuli in Neutrophils
Neeli, I., Khan, S. N., & Radic, M. Z. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.3.1895 · Cited by 565 · see citing works
Nuclear Localization of Peptidylarginine Deiminase V and Histone Deimination in Granulocytes
Nakashima, K., Hagiwara, T., & Yamada, M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m208795200 · Cited by 379 · see citing works
BACTERICIDAL ACTION OF HISTONE
Hirsch, J. G. (1958) · The Journal of Experimental Medicine · doi:10.1084/jem.108.6.925 · Cited by 365 · see citing works
Yost, C. C., Cody, M. J., Harris, E. S., Thornton, N. L., McInturff, A. M., Martinez, M. L., Chandler, N. B., Rodesch, C. K., Albertine, K. H., Petti, C. A., et al. (2009) · Blood · doi:10.1182/blood-2008-07-171629 · Cited by 363 · see citing works
Innate immunity turned inside-out: antimicrobial defense by phagocyte extracellular traps
von Köckritz‐Blickwede, M., & Nizet, V. (2009) · Journal of Molecular Medicine · doi:10.1007/s00109-009-0481-0 · Cited by 270 · see citing works
Increased PADI4 expression in blood and tissues of patients with malignant tumors
Chang, X., Han, J., Pang, L., Zhao, Y., Yang, Y. L., & Shen, Z. (2009) · BMC Cancer · doi:10.1186/1471-2407-9-40 · Cited by 255 · see citing works
Brown, D. T., Izard, T., & Misteli, T. (2006) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1050 · Cited by 193 · see citing works
Nizet, V. (2007) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2007.06.005 · Cited by 192 · see citing works
Expression of peptidylarginine deiminase type 4 (PAD4) in various tumors
Chang, X., & Han, J. (2005) · Molecular Carcinogenesis · doi:10.1002/mc.20169 · Cited by 186 · see citing works
Nakashima, K., Hagiwara, T., Ishigami, A., Nagata, S., Asaga, H., Kuramoto, M., Senshu, T., & Yamada, M. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.39.27786 · Cited by 184 · see citing works
Datta, V., Myskowski, S. M., Kwinn, L. A., Chiem, D. N., Varki, N. M., Kansal, R. G., Kotb, M., & Nizet, V. (2005) · Molecular Microbiology · doi:10.1111/j.1365-2958.2005.04583.x · Cited by 176 · see citing works
ETosis: A Novel Cell Death Pathway
Wartha, F., & Henriques-Normark, B. (2008) · Science Signaling · doi:10.1126/stke.121pe25 · Cited by 173 · see citing works
Neutrophil Isolation from Nonhuman Species
Siemsen, D. W., Małachowa, N., Schepetkin, I. A., Whitney, A. R., Kirpotina, L. N., Lei, B., DeLeo, F. R., & Quinn, M. T. (2014) · Methods in molecular biology · doi:10.1007/978-1-62703-845-4_3 · Cited by 92 · see citing works
Xiong, N., Kang, C., & Raulet, D. H. (2002) · Immunity · doi:10.1016/s1074-7613(02)00285-6 · Cited by 65 · see citing works
Self-citationNeutrophil Isolation From Nonhuman Species
Siemsen, D. W., Schepetkin, I. A., Kirpotina, L. N., Lei, B., & Quinn, M. T. (2007) · Methods in molecular biology · doi:10.1007/978-1-59745-467-4_3 · Cited by 59 · see citing works
Mann, P. B., Elder, K. D., Kennett, M. J., & Harvill, E. T. (2004) · Infection and Immunity · doi:10.1128/iai.72.11.6650-6658.2004 · Cited by 52 · see citing works
Self-citationYamada, R., & Yamamoto, K. (2007) · Nature Clinical Practice Rheumatology · doi:10.1038/ncprheum0592 · Cited by 38 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680 · see citing works
Neutrophil extracellular traps in immunity and disease
Papayannopoulos, V. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2017.105 · Cited by 3,428 · see citing works
The molecular machinery of regulated cell death
Tang, D., Kang, R., Berghe, T. V., Vandenabeele, P., & Kroemer, G. (2019) · Cell Research · doi:10.1038/s41422-019-0164-5 · Cited by 2,595 · see citing works
Neutrophil Function: From Mechanisms to Disease
Amulic, B., Cazalet, C., Hayes, G. L., Metzler, K. D., & Zychlinsky, A. (2012) · Annual Review of Immunology · doi:10.1146/annurev-immunol-020711-074942 · Cited by 1,695 · see citing works
Neutrophils, from marrow to microbes.
Borregaard, N. (2010) · Immunity · doi:10.1016/j.immuni.2010.11.011 · Cited by 1,550 · see citing works
The multifaceted functions of neutrophils
Mayadas, T. N., Cullere, X., & Lowell, C. A. (2014) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-020712-164023 · Cited by 1,356 · see citing works
Khandpur, R., Carmona‐Rivera, C., Vivekanandan‐Giri, A., Gizinski, A. M., Yalavarthi, S., Knight, J. S., Friday, S. C., Li, S., Patel, R. M., Subramanian, V., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005580 · Cited by 1,342 · see citing works
Diabetes primes neutrophils to undergo NETosis, which impairs wound healing
Wong, S. L., Demers, M., Martinod, K., Gallant, M., Wang, Y., Goldfine, A. B., Kahn, C. R., & Wagner, D. D. (2015) · Nature Medicine · doi:10.1038/nm.3887 · Cited by 1,264 · see citing works
Self-citationThe Neutrophil's Role During Health and Disease.
Liew, P., & Kubes, P. (2019) · Physiological Reviews · doi:10.1152/physrev.00012.2018 · Cited by 1,032 · see citing works
Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo
Yipp, B. G., Petri, B., Salina, D., Jenne, C. N., Scott, B. N. V., Zbytnuik, L. D., Pittman, K., Asaduzzaman, M., Wu, K., Meijndert, H. C., et al. (2012) · Nature Medicine · doi:10.1038/nm.2847 · Cited by 1,169 · see citing works
Neutrophil Extracellular Traps: Double-Edged Swords of Innate Immunity
Kaplan, M. J., & Radic, M. Z. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1201719 · Cited by 1,168 · see citing works
van der Poll, T., Shankar‐Hari, M., & Wiersinga, W. J. (2021) · Immunity · doi:10.1016/j.immuni.2021.10.012 · Cited by 1,063 · see citing works
Interplay between inflammation and thrombosis in cardiovascular pathology
Stark, K., & Massberg, S. (2021) · Nature Reviews Cardiology · doi:10.1038/s41569-021-00552-1 · Cited by 1,033 · see citing works
Neutrophil extracellular traps: Is immunity the second function of chromatin?
Brinkmann, V., & Zychlinsky, A. (2012) · Journal of Cell Biology · doi:10.1083/jcb.201203170 · Cited by 1,021 · see citing works
Yipp, B. G., & Kubes, P. (2013) · Blood · doi:10.1182/blood-2013-04-457671 · Cited by 998 · see citing works
DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25
Yang, L., Liu, Q., Zhang, X., Liu, X., Zhou, B., Chen, J., Huang, D., Li, J., Li, H., Chen, F., et al. (2020) · Nature · doi:10.1038/s41586-020-2394-6 · Cited by 986 · see citing works
Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps
Park, J., Wysocki, R. W., Amoozgar, Z., Maiorino, L., Fein, M. R., Jorns, J., Schott, A. F., Kinugasa-Katayama, Y., Lee, Y., Won, N. H., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aag1711 · Cited by 984 · see citing works
SARS-CoV-2–triggered neutrophil extracellular traps mediate COVID-19 pathology
Veras, F. P., Pontelli, M. C., Silva, C. M. S., Toller-Kawahisa, J. E., de Lima, M., Nascimento, D. C., Schneider, A. H., Caetité, D. B., Tavares, L., Paiva, I. M., et al. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20201129 · Cited by 924 · see citing works
Neutrophil extracellular traps promote deep vein thrombosis in mice
Brill, A. G., Fuchs, T. A., Savchenko, A. S., Thomas, G. M., Martinod, K., Meyer, S. F. D., Bhandari, A. A., & Wagner, D. D. (2011) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2011.04544.x · Cited by 900 · see citing works
Nauseef, W. M., & Borregaard, N. (2014) · Nature Immunology · doi:10.1038/ni.2921 · Cited by 893 · see citing works
Demers, M., Krause, D. S., Schatzberg, D., Martinod, K., Voorhees, J. R., Fuchs, T. A., Scadden, D. T., & Wagner, D. D. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1200419109 · Cited by 883 · see citing works
Thrombosis: tangled up in NETs
Martinod, K., & Wagner, D. D. (2013) · Blood · doi:10.1182/blood-2013-10-463646 · Cited by 875 · see citing works
Neutrophil ageing is regulated by the microbiome
Zhang, D., Chen, G., Manwani, D., Mortha, A., Xu, C., Faith, J. J., Burk, R. D., Kunisaki, Y., Jang, J.-E., Scheiermann, C., et al. (2015) · Nature · doi:10.1038/nature15367 · Cited by 839 · see citing works
Ferroptosis in infection, inflammation, and immunity
Chen, X., Kang, R., Kroemer, G., & Tang, D. (2021) · The Journal of Experimental Medicine · doi:10.1084/jem.20210518 · Cited by 828 · see citing works
Teijeira, Á., Garasa, S., Gato, M., Alfaro, C., Miguéliz, I., Cirella, A., de Andrea, C., Ochoa, M. C., Otano, I., Etxeberría, I., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.03.001 · Cited by 799 · see citing works
Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation
Lewis, H. D., Liddle, J., Coote, J., Atkinson, S. J., Barker, M. D., Bax, B. D., Bicker, K. L., Bingham, R. P., Campbell, M. J., Chen, Y. H., et al. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1735 · Cited by 794 · see citing works
Neutrophils and NETS in modulating acute and chronic inflammation
Castanheira, F. V. S., & Kubes, P. (2019) · Blood · doi:10.1182/blood-2018-11-844530 · Cited by 792 · see citing works
Metabolic reprogramming and epigenetic modifications on the path to cancer
Sun, L., Zhang, H., & Gao, P. (2021) · Protein & Cell · doi:10.1007/s13238-021-00846-7 · Cited by 796 · see citing works
Intravascular Neutrophil Extracellular Traps Capture Bacteria from the Bloodstream during Sepsis
McDonald, B., Urrutia, R., Yipp, B. G., Jenne, C. N., & Kubes, P. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.06.011 · Cited by 772 · see citing works
Harre, U., Georgess, D., Bang, H., Bozec, A., Axmann, R., Ossipova, E., Jakobsson, P., Baum, W., Nimmerjahn, F., Szarka, E., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci60975 · Cited by 732 · see citing works
Douda, D. N., Khan, M. A., Grasemann, H., & Palaniyar, N. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1414055112 · Cited by 696 · see citing works
Neutrophil Extracellular Traps and Its Implications in Inflammation: An Overview
Delgado‐Rizo, V., Martinez-Guzman, M. A., Íñiguez-Gutiérrez, L., García-Orozco, A., Alvarado‐Navarro, A., & Fafutis‐Morris, M. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00081 · Cited by 688 · see citing works
McDonald, B., Davis, R. P., Kim, S., Tse, M., Esmon, C. T., Kołaczkowska, E., & Jenne, C. N. (2017) · Blood · doi:10.1182/blood-2016-09-741298 · Cited by 666 · see citing works
Neutrophils as emerging therapeutic targets
Németh, T., Sperandio, M., & Mócsai, A. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0054-z · Cited by 657 · see citing works
Xiao, Y., Cong, M., Li, J., He, D., Wu, Q., Tian, P., Wang, Y., Yang, S., Liang, C., Liang, Y., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2020.12.012 · Cited by 654 · see citing works
Self-citationNoncanonical inflammasome signaling elicits gasdermin D–dependent neutrophil extracellular traps
Chen, K. W., Monteleone, M. M., Boucher, D., Sollberger, G., Ramnath, D., Condon, N. D., von Pein, J. B., Brož, P., Sweet, M. J., & Schroder, K. (2018) · Science Immunology · doi:10.1126/sciimmunol.aar6676 · Cited by 640 · see citing works
Cellular Mechanisms of NETosis
Thiam, H. R., Wong, S. L., Wagner, D. D., & Waterman, C. M. (2020) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-020520-111016 · Cited by 624 · see citing works
Host DNases prevent vascular occlusion by neutrophil extracellular traps
Jiménez-Alcázar, M., Rangaswamy, C., Panda, R., Bitterling, J., Simsek, Y., Long, A. T., Bilyy, R. O., Krenn, V., Renné, C., Renné, T., et al. (2017) · Science · doi:10.1126/science.aam8897 · Cited by 597 · see citing works
Shi, J., Knevel, R., Suwannalai, P., van der Linden, M. P. M., Janssen, G. M. C., van Veelen, P. A., Levarht, N. E. W., Mil, A. H. M. V. D. H., Cerami, A., Huizinga, T. W. J., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1114465108 · Cited by 595 · see citing works
Konig, M. F., Abusleme, L., Reinholdt, J., Palmer, R. J., Jr., Teles, R. P., Sampson, K., Rosen, A., Nigrovic, P. A., Sokolove, J. B., Giles, J. T., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aaj1921 · Cited by 592 · see citing works
Kolaczkowska, E., Jenne, C. N., Surewaard, B. G. J., Thanabalasuriar, A., Lee, W.-Y., Sanz, M.-J., Mowen, K., Opdenakker, G., & Kubes, P. (2015) · Nature Communications · doi:10.1038/ncomms7673 · Cited by 584 · see citing works
Circulating Histones Are Mediators of Trauma-associated Lung Injury
Abrams, S. T., Zhang, N., Manson, J., Liu, T., Dart, C., Baluwa, F., Wang, S. S., Brohi, K., Kipar, A., Yu, W., et al. (2012) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201206-1037oc · Cited by 583 · see citing works
Neutrophil Extracellular Traps in Atherosclerosis and Atherothrombosis
Döring, Y., Soehnlein, O., & Weber, C. (2017) · Circulation Research · doi:10.1161/circresaha.116.309692 · Cited by 579 · see citing works
NETosis: Molecular Mechanisms, Role in Physiology and Pathology
Vorobjeva, N. V., & Chernyak, B. V. (2020) · Biochemistry (Moscow) · doi:10.1134/s0006297920100065 · Cited by 559 · see citing works
Huang, H., Tohme, S. T., Al‐Khafaji, A. B., Tai, S., Loughran, P., Chen, L., Wang, S., Kim, J., Billiar, T. R., Wang, Y., et al. (2015) · Hepatology · doi:10.1002/hep.27841 · Cited by 542 · see citing works
Self-citationMartinod, K., Demers, M., Fuchs, T. A., Wong, S. L., Brill, A. G., Gallant, M., Hu, J., Wang, Y., & Wagner, D. D. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1301059110 · Cited by 532 · see citing works
Self-citationNeutrophil extracellular traps — the dark side of neutrophils
Sørensen, O. E., & Borregaard, N. (2016) · Journal of Clinical Investigation · doi:10.1172/jci84538 · Cited by 532 · see citing works
Neutrophil extracellular traps in systemic autoimmune and autoinflammatory diseases
Wigerblad, G., & Kaplan, M. J. (2022) · Nature reviews. Immunology · doi:10.1038/s41577-022-00787-0 · Cited by 519 · see citing works
Gould, T. J., Vu, T. T., Swystun, L. L., Dwivedi, D. J., Safiah, H. C., Weitz, J. I., & Liaw, P. C. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.304114 · Cited by 494 · see citing works
NETosis, complement, and coagulation: a triangular relationship
de Bont, C. M., Boelens, W. C., & Pruijn, G. J. M. (2018) · Cellular and Molecular Immunology · doi:10.1038/s41423-018-0024-0 · Cited by 493 · see citing works
Leshner, M., Wang, S., Lewis, C., Zheng, H., Chen, X. A., Santy, L. C., & Wang, Y. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00307 · Cited by 482 · see citing works
Self-citationWolach, O., Sellar, R. S., Martinod, K., Cherpokova, D., McConkey, M., Chappell, R. J., Silver, A. J., Adams, D., Castellano, C. A., Schneider, R. K., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aan8292 · Cited by 481 · see citing works
Neutrophils facilitate ovarian cancer premetastatic niche formation in the omentum
Lee, W., Ko, S. Y., Mohamed, M. S., Kenny, H. A., Lengyel, E., & Naora, H. (2019) · Journal of Experimental Medicine · doi:10.1084/jem.20181170 · Cited by 478 · see citing works
NET balancing: a problem in inflammatory lung diseases
Cheng, O. Z., & Palaniyar, N. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00001 · Cited by 453 · see citing works
Knight, J. S., Subramanian, V., O'Dell, A. A., Yalavarthi, S., Zhao, W., Smith, C. K., Hodgin, J. B., Thompson, P. R., & Kaplan, M. J. (2015) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2014-205365 · Cited by 443 · see citing works
Zhong, Q., Xiao, X., Qiu, Y., Xu, Z., Chen, C., Chong, B., Zhao, X., Hai, S., Li, S., An, Z., et al. (2023) · MedComm · doi:10.1002/mco2.261 · Cited by 442 · see citing works
Boeltz, S., Amini, P., Anders, H., Andrade, F., Bilyy, R. O., Chatfield, S. M., Cichoń, I., Clancy, D. M., Desai, J., Dumych, T. I., et al. (2019) · Cell Death and Differentiation · doi:10.1038/s41418-018-0261-x · Cited by 439 · see citing works
Thiam, H. R., Wong, S. L., Qiu, R., Kittisopikul, M., Vahabikashi, A., Goldman, A. E., Goldman, R. D., Wagner, D. D., & Waterman, C. M. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1909546117 · Cited by 438 · see citing works
The role of neutrophils and NETosis in autoimmune and renal diseases
Gupta, S., & Kaplan, M. J. (2016) · Nature Reviews Nephrology · doi:10.1038/nrneph.2016.71 · Cited by 433 · see citing works
Parker, H., Dragunow, M., Hampton, M. B., Kettle, A. J., & Winterbourn, C. C. (2012) · Journal of Leukocyte Biology · doi:10.1189/jlb.1211601 · Cited by 430 · see citing works
Neutrophil Extracellular Traps Participate in Cardiovascular Diseases
Döring, Y., Libby, P., & Soehnlein, O. (2020) · Circulation Research · doi:10.1161/circresaha.120.315931 · Cited by 415 · see citing works
Pathogenesis of pneumonia and acute lung injury
Long, M. E., Mallampalli, R. K., & Horowitz, J. C. (2022) · Clinical Science · doi:10.1042/cs20210879 · Cited by 410 · see citing works
Citrullination regulates pluripotency and histone H1 binding to chromatin
Christophorou, M. A., Castelo‐Branco, G., Halley‐Stott, R. P., Oliveira, C. S., Loos, R., Radzisheuskaya, A., Mowen, K. A., Bertone, P., Silva, J., Zernicka‐Goetz, M., et al. (2014) · Nature · doi:10.1038/nature12942 · Cited by 409 · see citing works
Neutrophil extracellular traps promote differentiation and function of fibroblasts
Chrysanthopoulou, A., Mitroulis, I., Apostolidou, E., Arelaki, S., Mikroulis, D. A., Konstantinidis, T. G., Sivridis, E., Koffa, M. D., Giatromanolaki, A. N., Boumpas, D. T., et al. (2014) · The Journal of Pathology · doi:10.1002/path.4359 · Cited by 408 · see citing works
Neutrophil Extracellular Traps
Thålin, C., Hisada, Y., Lundström, S., Mackman, N., & Wallén, H. (2019) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.119.312463 · Cited by 408 · see citing works
Activation of PAD4 in NET formation
Rohrbach, A. S., Slade, D. J., Thompson, P. R., & Mowen, K. A. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00360 · Cited by 404 · see citing works
Neutrophil extracellular traps regulate ischemic stroke brain injury
Denorme, F., Portier, I., Rustad, J. L., Cody, M. J., de Araujo, C. V., Hoki, C., Alexander, M. D., Grandhi, R., Dyer, M., Neal, M. D., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci154225 · Cited by 399 · see citing works
Wang, H., Zhang, H., Wang, Y., Brown, Z. J., Xia, Y., Huang, Z., Shen, C., Hu, Z., Beane, J., Ansa-Addo, E. A., et al. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2021.07.032 · Cited by 398 · see citing works
Self-citationPeptidylarginine deiminase inhibition is immunomodulatory and vasculoprotective in murine lupus
Knight, J. S., Zhao, W., Luo, W., Subramanian, V., O’Dell, A. A., Yalavarthi, S., Hodgin, J. B., Eitzman, D. T., Thompson, P. R., & Kaplan, M. J. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67390 · Cited by 388 · see citing works
Gut-derived low-grade endotoxaemia, atherothrombosis and cardiovascular disease
Violi, F., Cammisotto, V., Bartimoccia, S., Pignatelli, P., Carnevale, R., & Nocella, C. (2022) · Nature Reviews Cardiology · doi:10.1038/s41569-022-00737-2 · Cited by 384 · see citing works
Nakazawa, D., Kumar, S. V. R., Marschner, J. A., Desai, J., Holderied, A., Rath, L., Kraft, F., Lei, Y., Fukasawa, Y., Moeckel, G. W., et al. (2017) · Journal of the American Society of Nephrology · doi:10.1681/asn.2016080925 · Cited by 362 · see citing works
Metabolic requirements for neutrophil extracellular traps formation
Rodríguez‐Espinosa, O., Rojas-Espinosa, O., Moreno‐Altamirano, M. M. B., López‐Villegas, E. O., & Sánchez‐García, F. J. (2014) · Immunology · doi:10.1111/imm.12437 · Cited by 360 · see citing works
Tadié, J., Bae, H., Jiang, S., Park, D. W., Bell, C. P., Yang, H., Pittet, J., Tracey, K. J., Thannickal, V. J., Abraham, E. H., et al. (2013) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00151.2012 · Cited by 358 · see citing works
Heme-induced neutrophil extracellular traps contribute to the pathogenesis of sickle cell disease
Chen, G., Zhang, D., Fuchs, T. A., Manwani, D., Wagner, D. D., & Frenette, P. S. (2014) · Blood · doi:10.1182/blood-2013-10-529982 · Cited by 354 · see citing works
Chowdhury, C. S., Giaglis, S., Walker, U. A., Buser, A. S., Hahn, S., & Hasler, P. (2014) · Arthritis Research & Therapy · doi:10.1186/ar4579 · Cited by 352 · see citing works
Adrover, J. M., McDowell, S. A. C., He, X., Quail, D. F., & Egeblad, M. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.02.001 · Cited by 349 · see citing works
Neutrophil Extracellular Traps: The Biology of Chromatin Externalization
Sollberger, G., Tilley, D. O., & Zychlinsky, A. (2018) · Developmental Cell · doi:10.1016/j.devcel.2018.01.019 · Cited by 346 · see citing works
Emerging mechanisms of lipid peroxidation in regulated cell death and its physiological implications
Zheng, Y., Sun, J., Luo, Z., Li, Y., & Huang, Y. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-07244-x · Cited by 349 · see citing works
Neutrophil phenotypes and functions in cancer: A consensus statement
Quail, D. F., Amulic, B., Aziz, M., Barnes, B. J., Eruslanov, E. B., Fridlender, Z. G., Goodridge, H. S., Granot, Z., Hidalgo, A., Huttenlocher, A., et al. (2022) · The Journal of Experimental Medicine · doi:10.1084/jem.20220011 · Cited by 336 · see citing works
New Insights into Neutrophil Extracellular Traps: Mechanisms of Formation and Role in Inflammation
Yang, H., Biermann, M. H. C., Brauner, J., Liu, Y., Zhao, Y., & i, M. H. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00302 · Cited by 335 · see citing works
Neutrophil Extracellular Traps Sustain Inflammatory Signals in Ulcerative Colitis
Dinallo, V., Marafini, I., Fusco, D. D., Laudisi, F., Franzè, E., Grazia, A. D., Figliuzzi, M. M., Caprioli, F., Stolfi, C., Monteleone, I., et al. (2019) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjy215 · Cited by 331 · see citing works
Neutrophil Extracellular Trap Formation: Physiology, Pathology, and Pharmacology
Ravindran, M., Khan, M. A., & Palaniyar, N. (2019) · Biomolecules · doi:10.3390/biom9080365 · Cited by 328 · see citing works
Chemical Biology of Protein Arginine Modifications in Epigenetic Regulation
Fuhrmann, J., Clancy, K. W., & Thompson, P. R. (2015) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00003 · Cited by 325 · see citing works
Molecular mechanisms regulating NETosis in infection and disease
Branzk, N., & Papayannopoulos, V. (2013) · Seminars in Immunopathology · doi:10.1007/s00281-013-0384-6 · Cited by 319 · see citing works
Neutrophil Extracellular Traps in Pulmonary Diseases: Too Much of a Good Thing?
Porto, B. N., & Stein, R. T. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00311 · Cited by 317 · see citing works
Roles of PAD4 and NETosis in Experimental Atherosclerosis and Arterial Injury
Franck, G., Mawson, T. L., Folco, E. J. E., Molinaro, R., Ruvkun, V., Engelbertsen, D., Liu, X., Tesmenitsky, Y., Shvartz, E., Sukhova, G. K., et al. (2018) · Circulation Research · doi:10.1161/circresaha.117.312494 · Cited by 309 · see citing works
Extracellular DNA traps are associated with the pathogenesis of TRALI in humans and mice
Thomas, G. M., Carbó, C., Curtis, B. R., Martinod, K., Mazo, I. B., Schatzberg, D., Cifuni, S. M., Fuchs, T. A., von Andrian, U. H., Hartwig, J. H., et al. (2012) · Blood · doi:10.1182/blood-2012-01-405183 · Cited by 307 · see citing works
Neutrophils Versus Staphylococcus aureus : A Biological Tug of War
Spaan, A. N., Surewaard, B. G. J., Nijland, R., & van Strijp, J. A. G. (2013) · Annual Review of Microbiology · doi:10.1146/annurev-micro-092412-155746 · Cited by 305 · see citing works
Mauracher, L., Posch, F., Martinod, K., Grilz, E., Däullary, T., Hell, L., Brostjan, C., Zielinski, C. C., Ay, C., Wagner, D. D., et al. (2018) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.13951 · Cited by 307 · see citing works
Patients with COVID-19: in the dark-NETs of neutrophils
Ackermann, M., Anders, H., Bilyy, R. O., Bowlin, G. L., Daniel, C., LORENZO, R. D., Egeblad, M., Henneck, T., Hidalgo, A., Hoffmann, M. H., et al. (2021) · Cell Death and Differentiation · doi:10.1038/s41418-021-00805-z · Cited by 307 · see citing works
Programmed cell death and its role in inflammation
Yang, Y., Jiang, G., Zhang, P., & Fan, J. (2015) · Military Medical Research · doi:10.1186/s40779-015-0039-0 · Cited by 291 · see citing works
NETosis markers: Quest for specific, objective, and quantitative markers
Masuda, S., Nakazawa, D., Shida, H., Miyoshi, A., Kusunoki, Y., Tomaru, U., & Ishizu, A. (2016) · Clinica Chimica Acta · doi:10.1016/j.cca.2016.05.029 · Cited by 289 · see citing works
Savchenko, A. S., Borissoff, J. I., Martinod, K., Meyer, S. F. D., Gallant, M., Erpenbeck, L., Brill, A. G., Wang, Y., & Wagner, D. D. (2013) · Blood · doi:10.1182/blood-2013-07-514992 · Cited by 286 · see citing works
Self-citationNeutrophils in innate and adaptive immunity
Jaillon, S., Galdiero, M. R., Prete, D. D., Cassatella, M. A., Garlanda, C., & Mantovani, A. (2013) · Seminars in Immunopathology · doi:10.1007/s00281-013-0374-8 · Cited by 284 · see citing works
Programmed ‘disarming’ of the neutrophil proteome reduces the magnitude of inflammation
Adrover, J. M., Aroca-Crevillén, A., Crainiciuc, G., Ostos, F., Rojas-Vega, Y., Rubio-Ponce, A., Cillóniz, C., Bonzón‐Kulichenko, E., Calvo, E., Rico, D., et al. (2020) · Nature Immunology · doi:10.1038/s41590-019-0571-2 · Cited by 284 · see citing works
Neutrophil extracellular traps target senescent vasculature for tissue remodeling in retinopathy
Binet, F., Cagnone, G., Crespo-Garcia, S., Hata, M., Neault, M., Dejda, A., Wilson, A. M., Buscarlet, M., Mawambo, G. T., Howard, J. P., et al. (2020) · Science · doi:10.1126/science.aay5356 · Cited by 283 · see citing works
Peptidylarginine deiminases in citrullination, gene regulation, health and pathogenesis
Wang, S., & Wang, Y. (2013) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2013.07.003 · Cited by 283 · see citing works
Self-citationAlarcon, M. F., McLaren, Z., & Wright, H. L. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.649693 · Cited by 279 · see citing works
Neutrophil Extracellular Traps Drive Mitochondrial Homeostasis in Tumors to Augment Growth
Yazdani, H. O., Roy, E., Comerci, A. J., van der Windt, D. J., Zhang, H., Huang, H., Loughran, P., Shiva, S., Geller, D. A., Bartlett, D. L., et al. (2019) · Cancer Research · doi:10.1158/0008-5472.can-19-0800 · Cited by 277 · see citing works
Pre-metastatic niche: formation, characteristics and therapeutic implication
Wang, Y., Jia, J., Wang, F., Fang, Y., Yang, Y., Zhou, Q., Yuan, W., Gu, X., Hu, J., & Yang, S. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01937-7 · Cited by 275 · see citing works
Self-citation
- Authors
- Li, P., Li, M., Lindberg, M. R., Kennett, M. J., Xiong, N., & Wang, Y.
- Affiliations
- Pennsylvania State University (US)
- Corresponding author
- Wang, Yanming
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2010-08-23
- Volume
- 207
- Issue
- 9
- Pages
- 1853-1862
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2931169
- OpenAlex
- W2135849676
- Cited by
- 1,495
- References
- 31
- Citations by year
- 2026: 104 · 2025: 121 · 2024: 122 · 2023: 121 · 2022: 134 · 2021: 123 · 2020: 125 · 2019: 118 · 2018: 94 · 2017: 92 · 2016: 81 · 2015: 68 · 2014: 60 · 2013: 61 · 2012: 51
- FWCI
- 17.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (R01CA136856)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
- Keywords
- PAD4, neutrophil extracellular traps, neutrophils, chromatin decondensation, bacterial killing, necrotizing fasciitis, nucleosome
- MeSH terms
- Protein-Arginine Deiminase Type 4, Animals, Cell Differentiation, Dysentery, Bacillary, Extracellular Space, Histones, Hydrolases, Immunity, Innate, Neutrophils, Shigella flexneri, Mice, Knockout, Mice
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