{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T03:34:47Z","timestamp":1773372887043,"version":"3.50.1"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,2,4]],"date-time":"2020-02-04T00:00:00Z","timestamp":1580774400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,2,4]],"date-time":"2020-02-04T00:00:00Z","timestamp":1580774400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31741006"],"award-info":[{"award-number":["31741006"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2015A030310028"],"award-info":[{"award-number":["2015A030310028"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010909","name":"Young Scientists Fund","doi-asserted-by":"publisher","award":["81800428"],"award-info":[{"award-number":["81800428"]}],"id":[{"id":"10.13039\/501100010909","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Commun Signal"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Neutrophils form the first line of innate host defense against invading microorganisms. We previously showed that F0F1 ATP synthase (F-ATPase), which is widely known as mitochondrial respiratory chain complex V, is expressed in the plasma membrane of human neutrophils and is involved in regulating cell migration. Whether F-ATPase performs cellular functions through other pathways remains unknown.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Blue native polyacrylamide gel electrophoresis followed by nano-ESI-LC MS\/MS identification and bioinformatic analysis were used to identify protein complexes containing F-ATPase. Then, the identified protein complexes containing F-ATPase were verified by immunoblotting, immunofluorescence colocalization, immunoprecipitation, real-time RT-PCR and agarose gel electrophoresis. Immunoblotting, flow cytometry and a LPS-induced mouse lung injury model were used to assess the effects of the F-ATPase-containing protein complex in vitro and in vivo.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We found that the voltage-gated calcium channel (VGCC) \u03b12\u03b4-1 subunit is a binding partner of cell surface F-ATPase in human neutrophils. Further investigation found that the physical connection between the two proteins may exist between the F1 part (\u03b1 and \u03b2 subunits) of F-ATPase and the \u03b12 part of VGCC \u03b12\u03b4-1. Real-time RT-PCR and PCR analyses showed that Ca<jats:sub>v<\/jats:sub>2.3 (R-type) is the primary type of VGCC expressed in human neutrophils. Research on the F-ATPase\/Ca<jats:sub>v<\/jats:sub>2.3 functional complex indicated that it can regulate extracellular Ca<jats:sup>2+<\/jats:sup> influx, thereby modulating ERK1\/2 phosphorylation and reactive oxygen species production, which are typical features of neutrophil activation. In addition, the inhibition of F-ATPase can reduce neutrophil accumulation in the lungs of mice that were intratracheally instilled with lipopolysaccharide, suggesting that the inhibition of F-ATPase may prevent neutrophilic inflammation-induced tissue damage.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>In this study, we identified a mechanism by which neutrophil activity is modulated, with simultaneous regulation of neutrophil-mediated pulmonary damage. These results show that surface F-ATPase of neutrophils is a potential innate immune therapeutic target.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1186\/s12964-020-0515-3","type":"journal-article","created":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T00:06:45Z","timestamp":1612310805000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["F0F1 ATP synthase regulates extracellular calcium influx in human neutrophils by interacting with Cav2.3 and modulates neutrophil accumulation in the lipopolysaccharide-challenged lung"],"prefix":"10.1186","volume":"18","author":[{"given":"Baoyi","family":"Zhu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengfu","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ai","family":"Mai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhanfang","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Weijen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dazhong","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongxing","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0460-5624","authenticated-orcid":false,"given":"Jun","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,2,4]]},"reference":[{"key":"515_CR1","doi-asserted-by":"publisher","first-page":"1964","DOI":"10.4049\/jimmunol.170.4.1964","volume":"1704","author":"G Fossati","year":"2003","unstructured":"Fossati G, Moulding DA, Spiller DG, Moots RJ, White MR, Edwards SW. The mitochondrial network of human neutrophils: role in chemotaxis, phagocytosis, respiratory burst activation, and commitment to apoptosis. J Immunol. 2003;1704:1964\u201372.","journal-title":"J Immunol"},{"key":"515_CR2","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/sj.cdd.4401320","volume":"112","author":"NA Maianski","year":"2004","unstructured":"Maianski NA, Geissler J, Srinivasula SM, Alnemri ES, Roos D, Kuijpers TW. Functional characterization of mitochondria in neutrophils: a role restricted to apoptosis. Cell Death Differ. 2004;112:143\u201353.","journal-title":"Cell Death Differ"},{"key":"515_CR3","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1172\/JCI110647","volume":"703","author":"N Borregaard","year":"1982","unstructured":"Borregaard N, Herlin T. Energy metabolism of human neutrophils during phagocytosis. J Clin Invest. 1982;703:550\u20137.","journal-title":"J Clin Invest"},{"key":"515_CR4","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1042\/bj2170851","volume":"2173","author":"SW Edwards","year":"1984","unstructured":"Edwards SW, Hallett MB, Campbell AK. Oxygen-radical production during inflammation may be limited by oxygen concentration. Biochem J. 1984;2173:851\u20134.","journal-title":"Biochem J"},{"key":"515_CR5","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1111\/imm.12437","volume":"1452","author":"O Rodr\u00edguez-Espinosa","year":"2015","unstructured":"Rodr\u00edguez-Espinosa O, Rojas-Espinosa O, Moreno-Altamirano MM, L\u00f3pez-Villegas EO, S\u00e1nchez-Garc\u00eda FJ. Metabolic requirements for neutrophil extracellular traps formation. Immunology. 2015;1452:213\u201324.","journal-title":"Immunology"},{"key":"515_CR6","doi-asserted-by":"publisher","first-page":"26794","DOI":"10.1074\/jbc.M114.572495","volume":"28939","author":"Y Bao","year":"2014","unstructured":"Bao Y, Ledderose C, Seier T, Graf AF, Brix B, Chong E, Junger WG. Mitochondria regulate neutrophil activation by generating ATP for autocrine purinergic signaling. J Biol Chem. 2014;28939:26794\u2013803.","journal-title":"J Biol Chem"},{"key":"515_CR7","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1093\/jb\/mvr049","volume":"1496","author":"D Okuno","year":"2011","unstructured":"Okuno D, Iino R, Noji H. Rotation and structure of FoF1-ATP synthase. J Biochem. 2011;1496:655\u201364.","journal-title":"J Biochem"},{"key":"515_CR8","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1146\/annurev-biochem-060614-034124","volume":"841","author":"W Junge","year":"2015","unstructured":"Junge W, Nelson N. ATP synthase. Annu Rev Biochem. 2015;841:631\u201357.","journal-title":"Annu Rev Biochem"},{"key":"515_CR9","doi-asserted-by":"publisher","first-page":"98","DOI":"10.2144\/000113610","volume":"502","author":"SW Perry","year":"2011","unstructured":"Perry SW, Norman JP, Barbieri J, Brown EB, Gelbard HA. Mitochondrial membrane potential probes and the proton gradient: a practical usage guide. Biotechniques. 2011;502:98\u2013115.","journal-title":"Biotechniques"},{"key":"515_CR10","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/1477-5956-5-12","volume":"51","author":"D Jethwaney","year":"2007","unstructured":"Jethwaney D, Islam MR, Leidal KG, Bernabe BVD, Campbell KP, Nauseef WM, Gibson BW. Proteomic analysis of plasma membrane and secretory vesicles from human neutrophils. Proteome Sci. 2007;51:12.","journal-title":"Proteome Sci"},{"key":"515_CR11","first-page":"5575","volume":"2008","author":"SM Uriarte","year":"1808","unstructured":"Uriarte SM, Powell DW, Luerman GC, Merchant ML, Cummins TD, Jog NR, Ward RA, Mcleish KR. Comparison of proteins expressed on secretory vesicle membranes and plasma membranes of human neutrophils. J Immunol. 1808;2008:5575\u201381.","journal-title":"J Immunol"},{"key":"515_CR12","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1080\/07853890600928698","volume":"386","author":"SL Chi","year":"2006","unstructured":"Chi SL, Pizzo SV. Cell surface F1Fo ATP synthase: a new paradigm? Ann Med. 2006;386:429\u201338.","journal-title":"Ann Med"},{"key":"515_CR13","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1038\/emm.2004.60","volume":"365","author":"BW Kim","year":"2004","unstructured":"Kim BW, Choo HJ, Lee JW, Kim JH, Ko YG. Extracellular ATP is generated by ATP synthase complex in adipocyte lipid rafts. Exp Mol Med. 2004;365:476\u201385.","journal-title":"Exp Mol Med"},{"key":"515_CR14","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/nature01250","volume":"4216918","author":"LO Martinez","year":"2003","unstructured":"Martinez LO, Jacquet S, Esteve J-P, Rolland C, Cabez\u00f3n E, Champagne E. Ectopic \u03b2-chain of ATP synthase is an apolipoprotein A-I receptor in hepatic HDL endocytosis. Nature. 2003;4216918:75\u20139.","journal-title":"Nature"},{"key":"515_CR15","doi-asserted-by":"publisher","first-page":"6656","DOI":"10.1073\/pnas.131067798131067798","volume":"9812","author":"TL Moser","year":"2001","unstructured":"Moser TL, Kenan DJ, Ashley TA, Roy JA, Goodman MD, Misra UK, Cheek DJ, Pizzo SV. Endothelial cell surface F1-F0 ATP synthase is active in ATP synthesis and is inhibited by angiostatin. Proc Natl Acad Sci U S A. 2001;9812:6656\u201361. https:\/\/doi.org\/10.1073\/pnas.131067798131067798 [pii].","journal-title":"Proc Natl Acad Sci U S A"},{"key":"515_CR16","doi-asserted-by":"publisher","first-page":"2811","DOI":"10.1073\/pnas.96.6.2811","volume":"966","author":"TL Moser","year":"1999","unstructured":"Moser TL, Stack MS, Asplin I, Enghild JJ, Hojrup P, Everitt L, Hubchak S, Schnaper HW, Pizzo SV. Angiostatin binds ATP synthase on the surface of human endothelial cells. Proc Natl Acad Sci U S A. 1999;966:2811\u20136.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"515_CR17","first-page":"81","volume":"351","author":"SL Xing","year":"2010","unstructured":"Xing SL, Yan J, Yu Z-H, Zhu C-Q. Neuronal cell surface ATP synthase mediates synthesis of extracellular ATP and regulation of intracellular pH. Cell Biol Int. 2010;351:81\u20136.","journal-title":"Cell Biol Int"},{"key":"515_CR18","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1096\/fj.01-0651fje","volume":"162","author":"R Benelli","year":"2002","unstructured":"Benelli R, Morini M, Carrozzino F, Ferrari N, Minghelli S, Santi L, Cassatella M, Noonan DM, Albini A. Neutrophils as a key cellular target for angiostatin: implications for regulation of angiogenesis and inflammation. FASEB J. 2002;162:267\u20139.","journal-title":"FASEB J"},{"key":"515_CR19","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1002\/elps.201200243","volume":"342","author":"J Gao","year":"2013","unstructured":"Gao J, Li J, Feng C, Hu Z, Liu W, Liang S, Yin D. Isolation technique and proteomic analysis of the erythrocyte ghosts of red-eared turtle (Trachemys scripta). Electrophoresis. 2013;342:215\u201323. https:\/\/doi.org\/10.1002\/elps.201200243.","journal-title":"Electrophoresis"},{"key":"515_CR20","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.molimm.2017.08.004","volume":"90","author":"J Gao","year":"2017","unstructured":"Gao J, Zhang T, Kang Z, Ting W, Xu L, Yin D. The F0F1 ATP synthase regulates human neutrophil migration through cytoplasmic proton extrusion coupled with ATP generation. Mol Immunol. 2017;90:219\u201326.","journal-title":"Mol Immunol"},{"key":"515_CR21","first-page":"418","volume":"11","author":"W Ilka","year":"2006","unstructured":"Ilka W, Hans-Peter B, Hermann SG. Blue native PAGE. Nat Protoc. 2006;11:418\u201328.","journal-title":"Nat Protoc"},{"key":"515_CR22","first-page":"4237","volume":"11521","author":"C Jia","year":"2010","unstructured":"Jia C, Haiyang T, Nissim H, Jingsong X, Ye RD. Akt isoforms differentially regulate neutrophil functions. Blood. 2010;11521:4237\u201346.","journal-title":"Blood"},{"key":"515_CR23","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/nmeth.1322","volume":"65","author":"JR Wisniewski","year":"2009","unstructured":"Wisniewski JR, Zougman A, Nagaraj N, Mann M. Universal sample preparation method for proteome analysis. Nat Methods. 2009;65:359\u201362.","journal-title":"Nat Methods"},{"key":"515_CR24","first-page":"187","volume":"1996","author":"LJ van Pelt","year":"1912","unstructured":"van Pelt LJ, Van ZR, Weening RS, Roos D, Verhoeven AJ, Bolscher BG. Limitations on the use of dihydrorhodamine 123 for flow cytometric analysis of the neutrophil respiratory burst. J Immunol Methods. 1912;1996:187\u201396.","journal-title":"J Immunol Methods"},{"issue":"9","key":"515_CR25","doi-asserted-by":"publisher","first-page":"e269","DOI":"10.1371\/journal.pmed.0040269","volume":"4","author":"Shirley H. J Mei","year":"2007","unstructured":"Mei SHMS, Deng Y, Parker CH, Liles WC, Stewart DJ. Prevention of LPS-induced acute lung injury in mice by mesenchymal stem cells overexpressing angiopoietin 1. PLoS Med. 2007;9. https:\/\/doi.org\/10.1371\/journal.pmed.0040269.","journal-title":"PLoS Medicine"},{"key":"515_CR26","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1006\/abio.1995.1523","volume":"2311","author":"P Klement","year":"1995","unstructured":"Klement P, Nijtmans LGJ, Vandenbogert C, Houstek J. Analysis of oxidative phosphorylation complexes in cultured human fibroblasts and Amniocytes by blue-native-electrophoresis using Mitoplasts isolated with the help of Digitonin. Anal Biochem. 1995;2311:218\u201324.","journal-title":"Anal Biochem"},{"key":"515_CR27","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1152\/physrev.00018.2002","volume":"831","author":"E Perezreyes","year":"2003","unstructured":"Perezreyes E. Molecular physiology of low-voltage-activated T-type calcium channels. Physiol Rev. 2003;831:117\u201361.","journal-title":"Physiol Rev"},{"key":"515_CR28","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.ceca.2009.08.006","volume":"464","author":"A Andrade","year":"2009","unstructured":"Andrade A, Sandoval A, Gonz\u00e1lez-Ram\u00edrez R, Lipscombe D, Campbell KP, Felix R. The alpha(2)delta subunit augments functional expression and modifies the pharmacology of Ca(V)1.3 L-type channels. Cell Calcium. 2009;464:282\u201392.","journal-title":"Cell Calcium"},{"key":"515_CR29","first-page":"1","volume":"201","author":"T Yasuda","year":"2015","unstructured":"Yasuda T, Chen L, Barr W, Mcrory JE, Lewis RJ, Adams DJ, Zamponi GW. Auxiliary subunit regulation of high-voltage activated calcium channels expressed in mammalian cells. Eur J Neurosci. 2015;201:1\u201313.","journal-title":"Eur J Neurosci"},{"key":"515_CR30","doi-asserted-by":"publisher","first-page":"8979","DOI":"10.1073\/pnas.1403731111","volume":"11124","author":"JS Cassidy","year":"2014","unstructured":"Cassidy JS, Ferron L, Kadurin I, Pratt WS, Dolphin AC. Functional exofacially tagged N-type calcium channels elucidate the interaction with auxiliary \u03b12\u03b4-1 subunits. Proc Natl Acad Sci U S A. 2014;11124:8979\u201384.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"515_CR31","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1167\/iovs.03-0937","volume":"452","author":"L Baumann","year":"2004","unstructured":"Baumann L, Gerstner A, Zong X, Biel M, Wahlschott C. Functional characterization of the L-type Ca2+ channel Cav1.4\u03b11 from mouse retina. Invest Ophthalmol Vis Sci. 2004;452:708\u201313.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"515_CR32","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/ni.2258","volume":"135","author":"X Liu","year":"2012","unstructured":"Liu X, Ma B, Malik AB, Tang H, Yang T, Sun B, Wang G, Minshall RD, Li Y, Zhao Y. Bidirectional regulation of neutrophil migration by mitogen-activated protein kinases. Nat Immunol. 2012;135:457\u201364.","journal-title":"Nat Immunol"},{"key":"515_CR33","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.vetimm.2006.11.003","volume":"1153\u20134","author":"A Sandoval","year":"2007","unstructured":"Sandoval A, Trivi\u00f1os F, Sanhueza A, Carretta D, Hidalgo MA, Hancke JL, Burgos RA. Propionate induces pH (i) changes through calcium flux, ERK1\/2, p38, and PKC in bovine neutrophils. Vet Immunol Immunopathol. 2007;1153\u20134:286\u201398.","journal-title":"Vet Immunol Immunopathol"},{"key":"515_CR34","doi-asserted-by":"publisher","first-page":"18302","DOI":"10.1038\/srep18302","volume":"5","author":"NC Rochael","year":"2015","unstructured":"Rochael NC, Guimar\u00e3es-Costa AB, Nascimento MT, Desouza-Vieira TS, Oliveira MP, Lf GES, Oliveira MF, Saraiva EM. Classical ROS-dependent and early\/rapid ROS-independent release of neutrophil extracellular traps triggered by Leishmania parasites. Sci Rep. 2015;5:18302. https:\/\/doi.org\/10.1038\/srep18302.","journal-title":"Sci Rep"},{"issue":"435","key":"515_CR35","doi-asserted-by":"publisher","first-page":"eaal4045","DOI":"10.1126\/scitranslmed.aal4045","volume":"10","author":"Qingming Hou","year":"2018","unstructured":"Qingming Hou FL, 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;10435. https:\/\/doi.org\/10.1126\/scitranslmed.aal4045.","journal-title":"Science Translational Medicine"},{"key":"515_CR36","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1016\/j.tips.2007.03.005","volume":"285","author":"A Davies","year":"2007","unstructured":"Davies A, Hendrich J, Minh ATV, Wratten J, Douglas L, Dolphin AC. Functional biology of the \u03b12\u03b4 subunits of voltage-gated calcium channels. Trends Pharmacol Sci. 2007;285:220\u20138.","journal-title":"Trends Pharmacol Sci"},{"key":"515_CR37","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/S0896-6273(00)80061-6","volume":"162","author":"CA Gurnett","year":"1996","unstructured":"Gurnett CA, Waard MD, Campbell KP. Dual function of the voltage-dependent Ca 2+ channel \u03b1 2 \u03b4 subunit in current stimulation and subunit interaction. Neuron. 1996;162:431\u201340.","journal-title":"Neuron"},{"key":"515_CR38","doi-asserted-by":"publisher","first-page":"43802","DOI":"10.1038\/srep43802","volume":"7","author":"I Kadurin","year":"2017","unstructured":"Kadurin I, Rothwell SW, Lana B, NietoRostro M, Dolphin AC. LRP1 influences trafficking of N-type calcium channels via interaction with the auxiliary \u03b12\u03b4-1 subunit. Sci Rep. 2017;7:43802.","journal-title":"Sci Rep"},{"key":"515_CR39","doi-asserted-by":"publisher","first-page":"1956","DOI":"10.1016\/j.celrep.2018.01.073","volume":"228","author":"FX Zhang","year":"2018","unstructured":"Zhang FX, Gadotti VM, Souza IA, Chen L, Zamponi GW. BK potassium channels suppress Cav\u03b12\u03b4 subunit function to reduce inflammatory and neuropathic pain. Cell Rep. 2018;228:1956\u201364.","journal-title":"Cell Rep"},{"key":"515_CR40","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1016\/j.cell.2009.09.025","volume":"1392","author":"\u00c7 Eroglu","year":"2009","unstructured":"Eroglu \u00c7, Allen NJ, Susman MW, O'Rourke NA, Chan YP, \u00d6zkan E, Chakraborty C, Mulinyawe SB, Annis DS, Huberman AD. Gabapentin receptor \u03b12\u03b4-1 is a neuronal Thrombospondin receptor responsible for excitatory CNS synaptogenesis. Cell. 2009;1392:380\u201392.","journal-title":"Cell"},{"key":"515_CR41","doi-asserted-by":"publisher","first-page":"2307","DOI":"10.1016\/j.celrep.2018.02.021","volume":"229","author":"J Chen","year":"2018","unstructured":"Chen J, Li L, Chen SR, Chen H, Xie JD, Sirrieh RE, Maclean DM, Zhang Y, Zhou MH, Jayaraman V. The \u03b12\u03b4-1-NMDA receptor complex is critically involved in neuropathic pain development and gabapentin therapeutic actions. Cell Rep. 2018;229:2307\u201321.","journal-title":"Cell Rep"},{"key":"515_CR42","first-page":"5575","volume":"2008","author":"S Uriarte","year":"1808","unstructured":"Uriarte S, Powell D, Gc MM, Cummins T, Jog N, Ward R, Mcleish K. Comparison of proteins expressed on secretory vesicle membranes and plasma membranes of human neutrophils. J Immunol. 1808;2008:5575\u201381.","journal-title":"J Immunol"},{"key":"515_CR43","doi-asserted-by":"publisher","first-page":"788","DOI":"10.3390\/ph6070788","volume":"67","author":"G Gurkoff","year":"2013","unstructured":"Gurkoff G, Shahlaie K, Lyeth B, Berman R. Voltage-gated Calcium Channel antagonists and traumatic brain injury. Pharmaceuticals. 2013;67:788\u2013812.","journal-title":"Pharmaceuticals"},{"key":"515_CR44","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1172\/JCI109880","volume":"663","author":"BE Seligmann","year":"1980","unstructured":"Seligmann BE, Gallin JI. Use of lipophilic probes of membrane potential to assess human neutrophil activation. Abnormality in chronic granulomatous disease. J Clin Invest. 1980;663:493\u2013503.","journal-title":"J Clin Invest"},{"key":"515_CR45","doi-asserted-by":"crossref","first-page":"13248","DOI":"10.1016\/S0021-9258(17)38861-0","volume":"26024","author":"L Simchowitz","year":"1985","unstructured":"Simchowitz L. Chemotactic factor-induced activation of Na+\/H+ exchange in human neutrophils. II. Intracellular pH changes. J.biol.chem. 1985;26024:13248\u201355.","journal-title":"J.biol.chem"},{"key":"515_CR46","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1152\/ajpcell.00219.2007","volume":"2942","author":"H Hisayoshi","year":"2008","unstructured":"Hisayoshi H, Orit A, R Todd A, Nicolas T, Wendy F, John O, Sergio G. Na+\/H+ exchange and pH regulation in the control of neutrophil chemokinesis and chemotaxis. Am J Physiol-Cell Physiol. 2008;2942:526\u201334.","journal-title":"Am J Physiol-Cell Physiol"},{"key":"515_CR47","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1126\/science.2154036","volume":"2474943","author":"C Sardet","year":"1990","unstructured":"Sardet C, Counillon L, Franchi A, Pouyss\u00e9gur J. Growth factors induce phosphorylation of the Na+\/H+ Antiporter, a glycoprotein of 110 kD. Science. 1990;2474943:723\u20136.","journal-title":"Science"},{"key":"515_CR48","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/S0014-5793(02)02867-3","volume":"5211\u20133","author":"K Maly","year":"2002","unstructured":"Maly K, Strese K, Kampfer S, Ueberall F, Baier G, Ghaffari-Tabrizi N, Grunicke HH, Leitges M. Critical role of protein kinase C \u03b1 and calcium in growth factor induced activation of the Na + \/H + exchanger NHE1. FEBS Lett. 2002;5211\u20133:205\u201310.","journal-title":"FEBS Lett"},{"key":"515_CR49","doi-asserted-by":"crossref","first-page":"5583","DOI":"10.1016\/S0021-9258(17)37501-4","volume":"2698","author":"S Wakabayashi","year":"1994","unstructured":"Wakabayashi S, Bertrand B, Shigekawa M, Fafournoux P, Pouyss\u00e9gur J. Growth factor activation and \"H(+)-sensing\" of the Na+\/H+ exchanger isoform 1 (NHE1). Evidence for an additional mechanism not requiring direct phosphorylation. J Biol Chem. 1994;2698:5583\u20138.","journal-title":"J Biol Chem"},{"key":"515_CR50","doi-asserted-by":"crossref","first-page":"13710","DOI":"10.1016\/S0021-9258(17)36888-6","volume":"26918","author":"S Wakabayashi","year":"1994","unstructured":"Wakabayashi S, Bertrand B, Ikeda T, Pouyss\u00e9gur J, Shigekawa M. Mutation of calmodulin-binding site renders the Na+\/H+ exchanger (NHE1) highly H(+)-sensitive and Ca2+ regulation-defective. J Biol Chem. 1994;26918:13710\u20135.","journal-title":"J Biol Chem"},{"key":"515_CR51","first-page":"1792","volume":"3145806","author":"C Yu","year":"2006","unstructured":"Yu C, Ross C, Yoshiaki I, Linda Y, Naoyuki H, Annelies Z, Victor N, Paul AI, Wolfgang GJ. ATP release guides neutrophil chemotaxis via P2Y2 and A3 receptors. Science. 2006;3145806:1792\u20135.","journal-title":"Science"},{"key":"515_CR52","doi-asserted-by":"publisher","first-page":"H285","DOI":"10.1152\/ajpheart.2000.279.1.H285","volume":"2791","author":"K Yamamoto","year":"2000","unstructured":"Yamamoto K, Korenaga R, Kamiya A, Qi Z, Sokabe M, and Ando J. P2X(4) receptors mediate ATP-induced calcium influx in human vascular endothelial cells. Am J Physiol Heart Circ Physiol, 2000; 2791: H285.","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"515_CR53","doi-asserted-by":"publisher","first-page":"8363","DOI":"10.1523\/JNEUROSCI.22-19-08363.2002","volume":"2219","author":"YV Pankratov","year":"2002","unstructured":"Pankratov YV, Lalo UV, Krishtal OA. Role for P2X receptors in long-term potentiation. J Neurosci. 2002;2219:8363\u20139.","journal-title":"J Neurosci"},{"key":"515_CR54","first-page":"22650","volume":"28831","author":"B Yi","year":"2013","unstructured":"Yi B, Yu C, Carola L, Linglin L, Junger WG. Pannexin 1 channels link chemoattractant receptor signaling to local excitation and global inhibition responses at the front and back of polarized neutrophils. J Biol Chem. 2013;28831:22650\u20137.","journal-title":"J Biol Chem"},{"key":"515_CR55","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.tcm.2008.01.006","volume":"183","author":"HK Eltzschig","year":"2008","unstructured":"Eltzschig HK, Macmanus CF, Colgan SP. Neutrophils as sources of extracellular nucleotides: functional consequences at the vascular Interface. Trends Cardiovasc Med. 2008;183:103\u20137.","journal-title":"Trends Cardiovasc Med"},{"key":"515_CR56","first-page":"355","volume":"196","author":"A Luca","year":"2013","unstructured":"Luca A, P\u00e1l P. E Sylvester V, and Gy?Rgy H, CD39 and CD73 in immunity and inflammation. Trends Mol Med. 2013;196:355\u201367.","journal-title":"Trends Mol Med"},{"key":"515_CR57","doi-asserted-by":"publisher","first-page":"C526","DOI":"10.1152\/ajpcell.00219.2007","volume":"2942","author":"H Hayashi","year":"2008","unstructured":"Hayashi H, Aharonovitz O, Alexander RT, Touret N, Furuya W, Orlowski J, Grinstein S. Na+\/H+ exchange and pH regulation in the control of neutrophil chemokinesis and chemotaxis. Am J Phys Cell Phys. 2008;2942:C526\u201334. https:\/\/doi.org\/10.1152\/ajpcell.00219.2007.","journal-title":"Am J Phys Cell Phys"},{"key":"515_CR58","doi-asserted-by":"publisher","first-page":"1792","DOI":"10.1126\/science.1132559","volume":"3145806","author":"Y Chen","year":"2006","unstructured":"Chen Y, Corriden R, Inoue Y, Yip L, Hashiguchi N, Zinkernagel A, Nizet V, Insel PA, Junger WG. ATP release guides neutrophil chemotaxis via P2Y2 and A3 receptors. Science. 2006;3145806:1792\u20135. https:\/\/doi.org\/10.1126\/science.1132559.","journal-title":"Science"},{"key":"515_CR59","doi-asserted-by":"publisher","first-page":"28480","DOI":"10.1074\/jbc.M800039200","volume":"28342","author":"R Corriden","year":"2008","unstructured":"Corriden R, Chen Y, Inoue Y, Beldi G, Robson SC, Insel PA, Junger WG. Ecto-nucleoside triphosphate Diphosphohydrolase 1 (E-NTPDase1\/CD39) regulates neutrophil Chemotaxis by hydrolyzing released ATP to adenosine. J Biol Chem. 2008;28342:28480\u20136. https:\/\/doi.org\/10.1074\/jbc.M800039200.","journal-title":"J Biol Chem"},{"issue":"4Supple","key":"515_CR60","doi-asserted-by":"publisher","first-page":"S195","DOI":"10.1097\/01.CCM.0000057843.47705.E8","volume":"31","author":"E Abraham","year":"2003","unstructured":"Abraham E. Neutrophils and acute lung injury. Crit Care Med. 2003;31(4Supple):S195\u20139.","journal-title":"Crit Care Med"},{"key":"515_CR61","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/1465-9921-13-58","volume":"131","author":"JH Min","year":"2012","unstructured":"Min JH, Codipilly CN, Nasim S, Miller EJ, Ahmed MN. Synergistic protection against hyperoxia-induced lung injury by neutrophils blockade and EC-SOD overexpression. Respir Res. 2012;131:58. https:\/\/doi.org\/10.1186\/1465-9921-13-58.","journal-title":"Respir Res"},{"key":"515_CR62","doi-asserted-by":"publisher","first-page":"2661","DOI":"10.1172\/jci61303","volume":"1227","author":"A Caudrillier","year":"2012","unstructured":"Caudrillier A, Kessenbrock K, Gilliss BM, Nguyen JX, Marques MB, Monestier M, Toy P, Werb Z, Looney MR. Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury. J Clin Invest. 2012;1227:2661\u201371. https:\/\/doi.org\/10.1172\/jci61303.","journal-title":"J Clin Invest"},{"key":"515_CR63","doi-asserted-by":"publisher","first-page":"428","DOI":"10.4049\/jimmunol.1600766","volume":"2017","author":"P Sil","year":"1981","unstructured":"Sil P, Hayes CP, Reaves BJ, Breen P, Quinn S, Sokolove J, Rada B. P2Y6 receptor antagonist MRS2578 inhibits neutrophil activation and aggregated neutrophil extracellular trap formation induced by gout-associated monosodium Urate crystals. J Immunol. 1981;2017:428\u201342. https:\/\/doi.org\/10.4049\/jimmunol.1600766.","journal-title":"J Immunol"}],"container-title":["Cell Communication and Signaling"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-020-0515-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12964-020-0515-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-020-0515-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T00:26:30Z","timestamp":1612311990000},"score":1,"resource":{"primary":{"URL":"https:\/\/biosignaling.biomedcentral.com\/articles\/10.1186\/s12964-020-0515-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,4]]},"references-count":63,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["515"],"URL":"https:\/\/doi.org\/10.1186\/s12964-020-0515-3","relation":{},"ISSN":["1478-811X"],"issn-type":[{"value":"1478-811X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,4]]},"assertion":[{"value":"1 August 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 January 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 February 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The Institutional Review Board of the Sixth Affiliated Hospital of Guangzhou Medical University approved this work.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"19"}}