NEUTROPHIL EXTRACELLULAR TRAPS IN ACUTE PANCREATITIS
S. Chooklin1, S. Chuklin2, R. Barylyak1
- Lviv Regional Clinical Hospital, Ukraine
- St. Paraskeva Medical Center, Lviv, Ukraine
DOI: https://doi.org/10.15407/fz68.04.077
Abstract
The review focuses on the role of neutrophilic extracellular
traps (NETs) in the pathogenesis of acute pancreatitis. It is
shown that NETs can activate trypsin, cause inflammation and
pancreatic tissue damage, and clog the excretory ducts. NETs
are involved in the formation of gallstones, which are one
of the leading etiological factors of acute pancreatitis. NETs
also surround necrotic tissue in patients with severe acute
pancreatitis and contribute to further systemic inflammatory
response syndrome. The mechanisms of NETs formation in
acute pancreatitis, in particular, the importance of damageassociated molecular patterns, neutrophil microparticles, and
platelets in these processes are considered.
Keywords:
acute pancreatitis; neutrophils; neutrophil extracellular traps; platelets.
References
- Xiao AY, Tan ML, Wu LM, Asrani VM, Windsor JA, Yadav D, Petrov MS. Global incidence and mortality of pancreatic diseases: a systematic review, meta-analysis, and meta-regression of population-based cohort studies. Lancet Gastroenterol Hepatol. 2016;1:45-55.
CrossRef
- Crockett SD, Wani S, Gardner TB, Falck-Ytter Y, Barkun AN. American Gastroenterological Association Institute Guideline on Initial Management of Acute Pancreatitis. Gastroenterology. 2018;154:1096-1010.
CrossRef
PubMed
- van Dijk SM, Hallensleben NDL, van Santvoort HC, Fockens P, van Goor H, Bruno MJ, Besselink MG. Dutch pancreatitis study group. Acute pancreatitis: recent advances through randomized trials. Gut. 2017;66:2024-32.
CrossRef
PubMed
- Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, Tsiotos GG, Vege SS, Acute Pancreatitis Classification Working Group. Classification of acute pancreatitis-2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62:102-11.
CrossRef
PubMed
- Lee PJ, Papachristou GI. New insights into acute pancreatitis. Nat Rev Gastroenterol Hepatol 2019;16:479-96.
CrossRef
PubMed
- Lankisch PG, Apte M, Banks PA. Acute pancreatitis. Lancet. 2015;386:85-96.
CrossRef
- Gliem N, Ammer-Herrmenau C, Ellenrieder V, Neesse A. management of severe acute pancreatitis: an update. Digestion. 2021;102:503-7.
CrossRef
PubMed PubMedCentral
- Yang ZW, Meng XX, Xu P. Central role of neutrophil in the pathogenesis of severe acute pancreatitis. J Cell Mol Med. 2015;19:2513-20.
CrossRef
PubMed PubMedCentral
- Murthy P, Singhi AD, Ross MA, Loughran P, Paragomi P, Papachristou GI, et al. Enhanced neutrophil extracellular trap formation in acute pancreatitis contributes to disease severity and is reduced by chloroquine. Front Immunol. 2019 Jan 24;10:28.
CrossRef
PubMed PubMedCentral
- Regner S, Manjer J, Appelros S, Hjalmarsson C, Sadic J, Borgström A. Protease activation, pancreatic leakage, and inflammation in acute pancreatitis: differences between mild and severe cases and changes over the first three days. Pancreatology. 2008;8:600-7.
CrossRef
PubMed
- Wan J, Ren Y, Yang X, Li X, Xia L, Lu N. The role of neutrophils and neutrophil extracellular traps in acute pancreatitis. Front Cell Dev Biol. 2021 Jan 21;8:565758.
CrossRef
PubMed PubMedCentral
- Gukovsky I, Li N, Todoric J, Gukovskaya A, Karin M. Inflammation, autophagy, and obesity: common features in the pathogenesis of pancreatitis and pancreatic cancer. Gastroenterology. 2013;144:1199-209.
CrossRef
PubMed PubMedCentral
- Merza M, Hartman H, Rahman M, Hwaiz R, Zhang E, Renström E, et al. Neutrophil extracellular traps induce trypsin activation, inflammation, and tissue damage in mice with severe acute pancreatitis. Gastroenterology. 2015;149:1920-31.
CrossRef
PubMed
- Korhonen JT, Dudeja V, Dawra R, Kubes P, Saluja A. Neutrophil extracellular traps provide a grip on the enigmatic pathogenesis of acute pancreatitis. Gastroenterology. 2015;149:1682-5.
CrossRef
PubMed
- Leppkes M, Maueroder C, Hirth S, Nowecki S, Günther C, Billmeier U, et al. Externalized decondensed neutrophil chromatin occludes pancreatic ducts and drives pancreatitis. Nat Commun. 2016 Mar 11;7:10973.
CrossRef
PubMed PubMedCentral
- Szatmary P, Liu T, Wen L, Huang W, Awais M, Wang G, Toh CH, Sutton R. The role of neutrophil extracellular traps in acute pancreatitis. Pancreas. 2014;43:1413.
- Gupta AK, Joshi MB, Philippova M, Erne P, Hasler P, Hahn S, Resink TJ. Activated endothelial cells induce neutrophil extracellular traps and are susceptible to NETosis-mediated cell death. FEBS Lett. 2010;584:3193-7.
CrossRef
PubMed
- Awla D, Abdulla A, Syk I, Jeppsson B, Regnér S,Thorlacius H. Neutrophil-derived matrix metalloproteinase-9 is a potent activator of trypsinogen in acinar cells in acute pancreatitis. J Leukoc Biol. 2012;91:711-9.
CrossRef
PubMed
- Madhi R, Rahman M, Mörgelin M, Thorlacius H. c-Abl kinase regulates neutrophil extracellular trap formation, inflammation, and tissue damage in severe acute pancreatitis. J Leukoc Biol. 2019;106: 455-66.
CrossRef
PubMed
- Madhi R, Rahman M, Taha D, Mörgelin M, Thorlacius H. Targeting peptidylarginine deiminase reduces neutrophil extracellular trap formation and tissue injury in severe acute pancreatitis. J Cell Physiol. 2019; 234:11850-60.
CrossRef
PubMed
- Woodring PJ, Litwack ED, O'Leary DD, Lucero GR, Wang JY, Hunter T. Modulation of the F-actin cytoskeleton by c-Abl tyrosine kinase in cell spreading and neurite extension. J Cell Biol. 2002;156:879-92.
CrossRef
PubMed PubMedCentral
- Woodring PJ, Hunter T, Wang JY. Regulation of F-actindependent processes by the Abl family of tyrosine kinases. J Cell Sci. 2003;116:2613-26.
CrossRef
PubMed
- Dawra R, Sharif R, Phillips P, Dudeja V, Dhaulakhandi D, Saluja AK. Development of a new mouse model of acute pancreatitis induced by administration of L-arginine. Am J Physiol Gastrointest Liver Physiol. 2007;292:G1009-18.
CrossRef
PubMed
- Niederau C, Luthen R, Niederau MC, Grendell JH, Ferrell LD. Acute experimental hemorrhagic-necrotizing pancreatitis induced by feeding a choline-deficient, ethionine-supplemented diet. Methodology and standards. Eur Surg Res. 1992;24 (Suppl. 1):40-54.
CrossRef
PubMed
- Maueroder C, Mahajan A, Paulus S, Gosswein S, Hahn J, Kienhofer D, et al. Menage-a-Trois: the ratio of bicarbonate to CO2 and the pH regulate the capacity of neutrophils to form NETs. Front Immunol. 2016;7:583.
CrossRef
PubMed PubMedCentral
- Wang Y, Li M, Stadler S, Correll S, Li P, Wang D, et al. Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation. J Cell Biol. 2009;184:205-13.
CrossRef
PubMed PubMedCentral
- Daniel C, Leppkes M, Muñoz LE, Schley G, Schett G, Herrmann M. Extracellular DNA traps in inflammation, injury and healing. Nat Rev Nephrol. 2019;15:559-75.
CrossRef
PubMed
- Shaffer EA. Gallstone disease: Epidemiology of gallbladder stone disease. Best Pract Res Clin Gastroenterol. 2006;20:981-96.
CrossRef
PubMed
- Muñoz LE, Boeltz S, Bilyy R, Schauer C, Mahajan A, Widulin N, et al. Neutrophil extracellular traps initiate gallstone formation. Immunity. 2019;51:443-50.
CrossRef
PubMed
- Cho SK, Jung S, Lee KJ, Kim JW. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio can predict the severity of gallstone pancreatitis. BMC Gastroenterol. 2018,18:18.
CrossRef
PubMed PubMedCentral
- O'Neil LJ, Kaplan MJ. NETched in stone. Immunity. 2019;51:413-4.
CrossRef
PubMed
- Bilyy R, Fedorov V, Vovk V, Leppkes M, Dumych T, Chopyak V, SchettG, Herrmann M. Neutrophil extracellular traps form a barrier between necrotic and viable areas in acute abdominal inflammation. Front Immunol. 2016;7:424.
CrossRef
PubMed PubMedCentral
- Schauer C, Janko C, Munoz LE, Zhao Y, Kienhofer D, Frey B, et al. Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines. Nat Med. 2014;20:511-7.
CrossRef
PubMed
- Longstaff C, Varju I, Sotonyi P, Szabo L, Krumrey M, Hoell A, et al. Mechanical stability and fibrinolytic resistance of clots containing fibrin, DNA, and histones. J Biol Chem. 2013;288:6946-56.
CrossRef
PubMed PubMedCentral
- Mercer PF, Chambers RC. Coagulation and coagulation signalling in fibrosis. Biochim Biophys Acta. 2013; 1832:1018-27.
CrossRef
PubMed
- Linders J, Madhi R, Rahman M, Mörgelin M, Regner S, Brenner M, Wang P, Thorlacius H. Extracellular cold-inducible RNA-binding protein regulates neutrophil extracellular trap formation and tissue damage in acute pancreatitis. Lab Invest. 2020;100:1618-30.
CrossRef
PubMed
- De Leeuw F, Zhang T, Wauquier C, Huez G, Kruys V, Gueydan C. The cold-inducible RNA-binding protein migrates from the nucleus to cytoplasmic stress granules by a methylation-dependent mechanism and acts as a translational repressor. Exp Cell Res. 2007;313:4130-44.
CrossRef
PubMed
- Qiang X, Yang WL, Wu R, Zhou M, Jacob A, Dong W, et al. Cold-inducible RNA-binding protein (CIRP) triggers inflammatory responses in hemorrhagic shock and sepsis. Nat Med. 2013;19:1489-95.
CrossRef
PubMed PubMedCentral
- Zhou Y, Dong H, Zhong Y, Huang J, Lv J, Li J. The cold-inducible RNA-binding protein (CIRP) level in peripheral blood predicts sepsis outcome. PLoS One. 2015;10:e0137721.
CrossRef
PubMed PubMedCentral
- Yoo IS, Lee SY, Park CK, Lee JC, Kim Y, Yoo SJ, et al. Serum and synovial fluid concentrations of cold-inducible RNA-binding protein in patients with rheumatoid arthritis. Int J Rheum Dis. 2018;21:148-54.
CrossRef
PubMed
- Zhang F, Brenner M, Yang WL, Wang P. A cold-inducible RNA-binding protein (CIRP)-derived peptide attenuates inflammation and organ injury in septic mice. Sci Rep. 2018;8:3052.
CrossRef
PubMed PubMedCentral
- Ode Y, Aziz M, Jin H, Arif A, Nicastro JG, Wang P. Cold-inducible RNA-binding protein induces neutrophil extracellular traps in the lungs during sepsis. Sci Rep. 2019;9:6252.
CrossRef
PubMed PubMedCentral
- Gong JD, Qi XF, Zhang Y, Li HL. Increased admission serum cold-inducible RNA-binding protein concentration is associated with prognosis of severe acute pancreatitis. Clin Chim Acta. 2017;471:135-42.
CrossRef
PubMed
- Mareninova OA, Sendler M, Malla SR, Yakubov I, French SW, Tokhtaeva E, et al. Lysosome associated membrane proteins maintain pancreatic acinar cell homeostasis: LAMP-2 deficient mice develop pancreatitis. Cell Mol Gastroenterol Hepatol. 2015;1:678-94.
CrossRef
PubMed PubMedCentral
- Fortunato F, Bürgers H, Bergmann F, Rieger P, Büchler MW, Kroemer G, Werner J. Impaired autolysosome formation correlates with Lamp-2 depletion: role of apoptosis, autophagy, and necrosis in pancreatitis. Gastroenterology. 2009;137:350-60.
CrossRef
PubMed
- Tang S, Zhang Y, Yin SW, Gao XJ, Shi WW, Wang Y, et al. Neutrophil extracellular trap formation is associated with autophagy-related signalling in ANCA-associated vasculitis. Clin Exp Immunol. 2015;180:408-18.
CrossRef
PubMed PubMedCentral
- Wu X, Yang Z, Wang H, Zhao Y, Gao X, Zang B. Highmobility group box protein-1 induces acute pancreatitis through activation of neutrophil extracellular trap and subsequent production of IL-1β. Life Sci. 2021; 286:119231.
CrossRef
PubMed
- Yang, R., J. Tenhunen, Tonnessen TI. HMGB1 and histones play a significant role in inducing systemic inflammation and multiple organ dysfunctions in severe acute pancreatitis. Int J Inflam. 2017;2017:1817564.
CrossRef
PubMed PubMedCentral
- Kang R, Zhang Q, Hou W, Yan Z, Chen R, Bonaroti J, et al. Intracellular Hmgb1 inhibits inflammatory nucleosome release and limits acute pancreatitis in mice. Gastroenterology. 2014;146:1097-107.
CrossRef
PubMed PubMedCentral
- Zhang ZW, Zhang QY, Zhou MT, Liu NX, Chen TK, Zhu YF, Wu L. Antioxidant inhibits HMGB1 expression and reduces pancreas injury in rats with severe acute pancreatitis. Dig Dis Sci. 2010;55:2529-36.
CrossRef
PubMed
- Irie Y, Tsubota M, Ishikura H, Sekiguchi F, Terada Y, Tsujiuchi T, Liu K, Nishibori M, Kawabata A. Macrophage-derived HMGB1 as a pain mediator in the early stage of acute pancreatitis in mice: Targeting RAGE and CXCL12/CXCR4 axis. J Neuroimmun Pharmacol. 2017;12:693-707.
CrossRef
PubMed
- Amini P, Stojkov D, Felser A, Jackson CB, Courage C, Schaller A, et al. Neutrophil extracellular trap formation requires OPA1-dependent glycolytic ATP production. Nat Commun. 2018;9:2958.
CrossRef
PubMed PubMedCentral
- Rabolli V, Lison D, Huaux F. The complex cascade of cellular events governing inflammasome activation and IL-1beta processing in response to inhaled particles. Part Fibre Toxicol. 2016;13:40.
CrossRef
PubMed PubMedCentral
- Petrilli V, Dostert C, Muruve DA, Tschopp J. The inflammasome: a danger sensing complex triggering innate immunity. Current Opin Immunol. 2007;19:615-22.
CrossRef
PubMed
- Plazyo O, Romero R, Unkel R, Balancio A, Mial TN, Xu Y, Dong Z, Hassan SS, Gomez-Lopez N. HMGB1 induces an inflammatory response in the chorioamniotic membranes that is partially mediated by the inflammasome. Biol Reprod. 2016;95:130.
CrossRef
PubMed PubMedCentral
- Kim EJ, Park SY, Baek SE, Jang MA, Lee WS, Bae SS, Kim K, Kim CD. HMGB1 Increases IL-1beta production in vascular smooth muscle cells via NLRP3 inflammasome. Front Physiol. 2018;9:313.
CrossRef
PubMed PubMedCentral
- Hess C, Sadallah S, Hefti A, Landmann R, Schifferli JA. Ectosomes released by human neutrophils are specialized functional units. J Immunol. 1999;163:4564-73.
- Madhi R, Rahman M, Taha D, Linders J, Merza M, Wang Y, Mörgelin M, Thorlacius H. Platelet IP6K1 regulates neutrophil extracellular trap-microparticle complex formation in acute pancreatitis. JCI Insight. 2021 6:e148169.
CrossRef
PubMed PubMedCentral
- Wang Y, L Luo, OÖ Braun, Westman J, Madhi R, Herwald H, Mörgelin M, Thorlacius H. Neutrophil extracellular trap-microparticle complexes enhance thrombin generation via the intrinsic pathway of coagulation in mice. Sci Rep. 2018;8:4020.
CrossRef
PubMed PubMedCentral
- Tokoro T, Makino I, Harada S, Okamoto K, Nakanuma S, Sakai S, et al. Interactions between neutrophils and platelets in the progression of acute pancreatitis. Pancreas. 2020;49:830-6.
CrossRef
PubMed
- Phillipson M, Kubes P. The neutrophil in vascular inflammation. Nature Med. 2011;17:1381-90.
CrossRef
PubMed PubMedCentral
- Sunamura M, Yamauchi J, Shibuya K, Chen HM, Ding L, Takeda K, Kobari M, Matsuno S. Pancreatic microcirculation in acute pancreatitis. J Hepatobiliar Pancreat Surg. 1998;5:62-8.
CrossRef
PubMed
- Hoque R, Sohail M, Malik A, Sarwar S, Luo Y, Shah A, Barrat F, Flavell R, Gorelick F, Husain S, Meha W. TLR9 and the NLRP3 inflammasome link acinar cell death with inflammation in acute pancreatitis. Gastroenterology. 2011;141:358-69.
CrossRef
PubMed PubMedCentral
- Kumble KD, Kornberg A. Inorganic polyphosphate in mammalian cells and tissues. J Biol Chem. 1995;270: 5818-22.
CrossRef
PubMed
- Ghosh S, Shukla D, Suman K, Lakshmi BJ, Manorama R, Kumar S, Bhandari R. Inositol hexakisphosphate kinase 1 maintains hemostasis in mice by regulating platelet polyphosphate levels. Blood. 2013;122:1478-86.
CrossRef
PubMed
- Hou Q, Liu F, Chakraborty A, Jia Y, Prasad A, Yu H, Zhao L, Ye K, Snyder SH, Xu Y, Luo HR. Inhibition of IP6K1 suppresses neutrophil-mediated pulmonary damage in bacterial pneumonia. Sci Transl Med. 2018 Apr 4;10(435):eaal4045.
CrossRef
PubMed PubMedCentral
- Kim SJ, Jenne CN. Role of platelets in neutrophil extracellular trap (NET) production and tissue injury. Semin Immunol. 2016;28:546-54.
CrossRef
PubMed
- Saffarzadeh M, Juenemann C, Queisser MA, Lochnit G, Barreto G, Galuska SP, Lohmeyer J, Preissner KT. Neutrophil extracellular traps directly induce epithelial and endothelial cell death: a predominant role of histones. PLoS One. 2012;7:e32366.
CrossRef
PubMed PubMedCentral
- Clark SR, Ma AC, Tavener SA, McDonald B, Goodarzi Z, Kelly MM, et al. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med. 2007;13:463-9.
CrossRef
PubMed
- Awla D, Abdulla A, Regner S, Thorlacius H. TLR4 but not TLR2 regulates inflammation and tissue damage in acute pancreatitis induced by retrograde infusion of taurocholate. Inflamm Res. 2011;60:1093-8.
CrossRef
PubMed
- Qi Q, Yang B, Li H, Bao J, Li H, Wang B, Mei Q. Platelet microparticles regulate neutrophil extracellular traps in acute pancreatitis. Pancreas. 2020;49:1099-103.
CrossRef
PubMed
- Abdulla A, Awla D, Hartman H, Rahman M, Jeppsson B, Regnér S, Thorlacius H. Role of platelets in experimental acute pancreatitis. Br J Surg. 2011;98:93-103.
CrossRef
PubMed
- Pieterse E, Rother N, Yanginlar C, Hilbrands LB, van der Vlag J. Neutrophils discriminate between lipopolysaccharides of different bacterial sources and selectively release neutrophil extracellular traps. Front Immunol. 2016;7:484.
CrossRef
PubMed PubMedCentral
- Jiang L, DingW, Zhang M. The progressive increase of the platelet count in a patient with acute severe pancreatitis. Am J Emerg Med. 2017;35:191. e1-191.e2.
CrossRef
PubMed
- Morel O, Toti F, Jesel L, Freyssinet JM. Mechanisms of microparticle generation: on the trail of the mitochondrion. Semin Thromb Hemost. 2010;36:833-44.
CrossRef
PubMed
- Nomura S, Ozaki Y, Ikeda Y. Function and role of microparticles in various clinical settings. Thromb Res. 2008;123:8-23.
CrossRef
PubMed
- Martínez MC, Tesse A, Zobairi F. Shed membrane microparticles from circulating and vascular cells in regulating vascular function. Am J Physiol Heart Circ Physiol. 2005;288:H1004-09.
CrossRef
PubMed
- Wetterholm E, Linders J, MerzaM, Regner S, Thorlacius H. Platelet-derived CXCL4 regulates neutrophil infiltration and tissue damage in severe acute pancreatitis. Transl Res. 2016;176:105-18.
CrossRef
PubMed
- Puddu P, Puddu GM, Cravero E, Muscari S, Muscari A. The involvement of circulating microparticles in inflammation, coagulation and cardiovascular diseases. Can J Cardiol. 2010;26:140-5.
CrossRef
- Prokopi M, Mayr M. Proteomics: a reality-check for putative stem cells. Circ Res. 2011;108:499-511.
CrossRef
PubMed
|