{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:00:42Z","timestamp":1792112442788,"version":"4.4.0"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T00:00:00Z","timestamp":1573430400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T00:00:00Z","timestamp":1573430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/15036-1"],"award-info":[{"award-number":["2017\/15036-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The role of neutrophils in cancer is still very contradictory. Several studies have demonstrated the cytotoxic capacity of neutrophils against different types of tumors, by releasing inflammatory cytokines, ROS and activating other immune cells. On the other hand, recent papers have claimed the protumorigenic action of neutrophils, mainly by changing their phenotype and producing cytokines that promote tumor growth. In this context, this study aimed to evaluate neutrophil action and function during tumor development. To do so, we used male Wistar rats inoculated with Walker 256 breast carcinoma. Tumor, circulating neutrophils and bone marrow were studied in the following time points after tumor inoculation: 12\u2009h, 24\u2009h, 48\u2009h, 3 d, 5 d, 7 d, 10 d, and 14 d, in order to analyze neutrophil migration kinetics, circulating neutrophil phenotype and bone marrow response to the tumor growth. Herein, our results demonstrated that W256T was unable to trigger an intratumoral inflammatory response after 5 days of tumor development and consequently, from that point on, prevented neutrophil migration to its microenvironment. Also, the tumor changed circulating neutrophil phenotype by up-regulating inflammation-related genes. Even though circulating neutrophils were entirely able to respond to an inflammatory stimulus, they did not recognize and attack the tumor, allowing the tumor to grow without any immune interference. To promote the entry of neutrophils into the tumor microenvironment, LPS was injected intratumorally. Neutrophil migration and activation due to LPS injection resulted in complete tumor regression in all subjects. In conclusion, activating neutrophils, within the tumor, turned the carcinoma into a recognizable immune target and eliminated it.<\/jats:p>","DOI":"10.1038\/s41598-019-52956-2","type":"journal-article","created":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T11:03:16Z","timestamp":1573470196000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Neutrophil activation causes tumor regression in Walker 256 tumor-bearing rats"],"prefix":"10.1038","volume":"9","author":[{"given":"Wilson Mitsuo Tatagiba","family":"Kuwabara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9ssica","family":"Andrade-Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joice Naiara Bertaglia","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julieta Helena","family":"Scialfa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Cipolla-Neto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,11]]},"reference":[{"issue":"4","key":"52956_CR1","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1189\/jlb.1112596","volume":"94","author":"Andrea Cerutti","year":"2013","unstructured":"Cerutti, A., Puga, I. & Magri, G. The B cell helper side of neutrophils. J Leukoc Biol. 2013 Oct; 94(4), 677\u201382, https:\/\/doi.org\/10.1189\/jlb.1112596 Epub 2013 Apr 29.","journal-title":"Journal of Leukocyte Biology"},{"key":"52956_CR2","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1172\/JCI103750","volume":"37","author":"DM Donohue","year":"1958","unstructured":"Donohue, D. M., Reiff, R. H., Hanson, M. L., Betson, Y. & Finch, C. A. Quantitative measurement of the erythrocytic and granulocytic cells of the marrow and blood. J. Clin. Invest. 37, 1571\u20131576 (1958).","journal-title":"J. Clin. Invest."},{"key":"52956_CR3","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1136\/jcp.10.3.267","volume":"10","author":"HD Suit","year":"1957","unstructured":"Suit, H. D. A technique for estimating the bone marrow cellularity in vivo using 59Fe. J. Clin. Pathol. 10, 267\u2013269 (1957).","journal-title":"J. Clin. Pathol."},{"issue":"8","key":"52956_CR4","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/j.it.2010.05.006","volume":"31","author":"Charlotte Summers","year":"2010","unstructured":"Summers, C. et al. Neutrophil kinetics in health and disease. Trends Immunol. 31(8), 318\u201324 (2010 Aug).","journal-title":"Trends in Immunology"},{"issue":"4","key":"52956_CR5","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1189\/jlb.1112571","volume":"94","author":"Tamar Tak","year":"2013","unstructured":"Tak, T., Tesselaar, K., Pillay, J., Borghans, J. A. & Koenderman, L. What\u2019s your age again? Determination of human neutrophil half-lives revisited. J Leukoc Biol. 94(4), 595\u2013601, https:\/\/doi.org\/10.1189\/jlb.1112571 (2013 Oct).","journal-title":"Journal of Leukocyte Biology"},{"key":"52956_CR6","doi-asserted-by":"publisher","first-page":"3377","DOI":"10.1038\/sj.onc.1205324","volume":"21","author":"AD Friedman","year":"2002","unstructured":"Friedman, A. D. Transcriptional regulation of granulocyte and monocyte development. Oncogene. 21, 3377\u20133390 (2002).","journal-title":"Oncogene."},{"key":"52956_CR7","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.exphem.2004.08.015","volume":"33","author":"AG Rosmarin","year":"2005","unstructured":"Rosmarin, A. G. Transcriptional regulation in myelopoiesis: hematopoietic fate choice, myeloid differentiation, and leukemogenesis. Exp. Hematol. 33, 131\u2013143 (2005).","journal-title":"Exp. Hematol."},{"key":"52956_CR8","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1073\/pnas.95.2.708","volume":"95","author":"DC Macallan","year":"1998","unstructured":"Macallan, D. C. et al. Measurement of cell proliferation by labeling of DNA with stable isotope-labeled glucose: studies in vitro, in animals, and in humans. Proc. Natl. Acad. Sci. USA 95, 708\u2013713 (1998).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"52956_CR9","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/S1074-7613(00)80046-1","volume":"10","author":"Q Ma","year":"1999","unstructured":"Ma, Q. The chemokine receptor CXCR4 is required for the retention of B lineage and granulocytic precursors within the bone marrow microenvironment. Immunity. 10, 463\u2013471 (1999).","journal-title":"Immunity."},{"key":"52956_CR10","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.exphem.2004.11.008","volume":"33","author":"LM Pelus","year":"2005","unstructured":"Pelus, L. M. The CXCR4 agonist peptide, CTCE-0021, rapidly mobilizes polymorphonuclear neutrophils and hematopoietic progenitor cells into peripheral blood and synergizes with granulocyte colony-stimulating factor. Exp. Hematol. 33, 295\u201330 (2005).","journal-title":"Exp. Hematol."},{"key":"52956_CR11","doi-asserted-by":"publisher","first-page":"604","DOI":"10.4049\/jimmunol.182.1.604","volume":"182","author":"JM Petty","year":"2009","unstructured":"Petty, J. M. Crosstalk between CXCR4\/stromal derived factor-1 and VLA-4\/VCAM-1 pathways regulates neutrophil retention in the bone marrow. J. Immunol. 182, 604\u2013612 (2009).","journal-title":"J. Immunol."},{"key":"52956_CR12","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1172\/JCI104338","volume":"40","author":"JW Athens","year":"1961","unstructured":"Athens, J. W. et al. Leukokinetic studies. IV. The total blood, circulating and marginal granulocyte pools and the granulocyte turnover rate in normal subjects. J. Clin. Invest. 40, 989\u2013995 (1961).","journal-title":"J. Clin. Invest."},{"key":"52956_CR13","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1111\/j.1365-2141.1985.tb02882.x","volume":"61","author":"SH Saverymuttu","year":"1985","unstructured":"Saverymuttu, S. H., Peters, A. M., Keshavarzian, A., Reavy, H. J. & Lavender, J. P. The kinetics of 111indium distribution following injection of 111indium labelled autologous granulocytes in man. Br. J. Haematol. 61, 675\u2013685 (1985).","journal-title":"Br. J. Haematol."},{"key":"52956_CR14","doi-asserted-by":"publisher","first-page":"865","DOI":"10.4049\/jimmunol.0804080","volume":"183","author":"S von Vietinghoff","year":"2009","unstructured":"von Vietinghoff, S. & Ley, K. IL-17A controls IL-17F production and maintains blood neutrophil counts in mice. J. Immunol. 183, 865\u2013873 (2009).","journal-title":"J. Immunol."},{"key":"52956_CR15","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.immuni.2005.01.011","volume":"22","author":"MA Stark","year":"2005","unstructured":"Stark, M. A. et al. Phagocytosis of apoptotic neutrophils regulates granulopoiesis via IL-23 and IL-17. Immunity 22, 285\u2013294 (2005).","journal-title":"Immunity"},{"key":"52956_CR16","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/ni.2260","volume":"13","author":"MA Eskan","year":"2012","unstructured":"Eskan, M. A. et al. The leukocyte integrin antagonist Del-1 inhibits IL-17-mediated inflammatory bone loss. Nat. Immunol. 13, 465\u2013473 (2012).","journal-title":"Nat. Immunol."},{"key":"52956_CR17","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1146\/annurev-pathol-011110-130318","volume":"8","author":"CT Weaver","year":"2013","unstructured":"Weaver, C. T., Elson, C. O., Fouser, L. A. & Kolls, J. K. The Th17 pathway and inflammatory diseases of the intestines, lungs, and skin. Annu. Rev. Pathol. 8, 477\u2013512 (2013).","journal-title":"Annu. Rev. Pathol."},{"issue":"69","key":"52956_CR18","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1111\/prd.12083","volume":"2000","author":"C Zenobia","year":"2015","unstructured":"Zenobia, C. & Hajishengallis, G. Basic biology and role of interleukin-17 in immunity and inflammation. Periodontol. 2000(69), 142\u2013159 (2015).","journal-title":"Periodontol."},{"key":"52956_CR19","doi-asserted-by":"crossref","unstructured":"Lawrence, S. M., Corriden, R. & Nizet, V. The Ontogeny of a Neutrophil: Mechanisms of Granulopoiesis and Homeostasis. Microbiol Mol Biol Rev, 82(1) (2018 Feb 7).","DOI":"10.1128\/MMBR.00057-17"},{"key":"52956_CR20","unstructured":"Urbaschek, R., M\u00e4nnel, D. N. & Urbaschek, B. Tumor necrosis factor induced stimulation of granulopoiesis and radioprotection. Lymphokine Res. Summer 6(3), 179\u201386 (1987)."},{"key":"52956_CR21","doi-asserted-by":"crossref","unstructured":"Liu, F., Poursine-Laurent, J., Wu, H. Y. & Link, D. C. Interleukin-6 and the granulocyte colony-stimulating factor receptor are major independent regulators of granulopoiesis in vivo but are not required for lineage commitment or terminal differentiation. Blood. 90(7), 2583\u201390 (1997 Oct 1).","DOI":"10.1182\/blood.V90.7.2583.2583_2583_2590"},{"key":"52956_CR22","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1038\/nature07205","volume":"454","author":"A Mantovani","year":"2008","unstructured":"Mantovani, A., Allavena, P., Sica, A. & Balkwill, F. Cancer-related inflammation. Nature 454, 436\u201344 (2008).","journal-title":"Nature"},{"issue":"5","key":"52956_CR23","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1038\/s41591-018-0014-x","volume":"24","author":"Mikhail Binnewies","year":"2018","unstructured":"Binnewies, M. et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat Med. 2018 May; 24(5), 541\u2013550, https:\/\/doi.org\/10.1038\/s41591-018-0014-x Epub (2018 Apr 23).","journal-title":"Nature Medicine"},{"key":"52956_CR24","doi-asserted-by":"crossref","unstructured":"Aras, S. & Zaidi, M. R. TAMeless traitors: macrophages in cancer progression and metastasis. Br J Cancer, 117(11), 1583\u20131591 (2017 Nov 21).","DOI":"10.1038\/bjc.2017.356"},{"issue":"5","key":"52956_CR25","doi-asserted-by":"publisher","first-page":"651","DOI":"10.7150\/ijbs.7.651","volume":"7","author":"BF Zamarron","year":"2011","unstructured":"Zamarron, B. F. & WanJun, C. Dual Roles of Immune Cells and Their Factors in Cancer Development and Progression. Int J Biol Sci. 7(5), 651\u2013658 (2011).","journal-title":"Int J Biol Sci."},{"issue":"3","key":"52956_CR26","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.ccr.2009.06.017","volume":"16","author":"Zvi G. Fridlender","year":"2009","unstructured":"Fridlender, Z. G. et al. Polarization of tumor-associated neutrophil phenotype by TGF-beta: \u201cN1\u201d versus \u201cN2\u201d TAN. Cancer Cell, 16(3), 183\u201394, https:\/\/doi.org\/10.1016\/j.ccr.2009.06.017 (2009 Sep 8).","journal-title":"Cancer Cell"},{"key":"52956_CR27","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1189\/jlb.1209793","volume":"88","author":"J Pillay","year":"2010","unstructured":"Pillay, J. et al. Functional heterogeneity and differential priming of circulating neutrophils in human experimental endotoxemia. J Leukoc Biol. 88, 211\u2013220, https:\/\/doi.org\/10.1189\/jlb.1209793 (2010).","journal-title":"J Leukoc Biol."},{"issue":"12","key":"52956_CR28","doi-asserted-by":"publisher","first-page":"e0189622","DOI":"10.1371\/journal.pone.0189622","volume":"12","author":"Wilson Mitsuo Tatagiba Kuwabara","year":"2017","unstructured":"Kuwabara, W. M. T. et al. Comparison of Goto-Kakizaki rats and high fat diet-induced obese rats: Are they reliable models to study Type 2 Diabetes mellitus? PLoS One. 12(12), https:\/\/doi.org\/10.1371\/journal.pone.0189622 (2017).","journal-title":"PLOS ONE"},{"key":"52956_CR29","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/j.ab.2010.02.036","volume":"15","author":"I Romero-Calvo","year":"2010","unstructured":"Romero-Calvo, I. et al. Reversible Ponceau staining as a loading control alternative to actin in Western blots. Anal Biochem. 15, 318\u2013320 (2010).","journal-title":"Anal Biochem."},{"key":"52956_CR30","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/0003-2697(87)90021-2","volume":"162","author":"P Chomczynski","year":"1987","unstructured":"Chomczynski, P. & Sacchi, N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 162, 56\u201359 (1987).","journal-title":"Anal Biochem."},{"key":"52956_CR31","doi-asserted-by":"publisher","unstructured":"Kuwabara, W. M. T., Yokota, C. N. F., Curi, R., Alba-Loureiro, T. C. Obesity and Type 2 Diabetes mellitus induce lipopolysaccharide tolerance in rat neutrophils. Sci Rep, 8(1), 17534, https:\/\/doi.org\/10.1038\/s41598-018-35809-2 (2018 Dec 3).","DOI":"10.1038\/s41598-018-35809-2"},{"key":"52956_CR32","doi-asserted-by":"crossref","unstructured":"Park, J. et al. Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps. Sci Transl Med, 8(361), 361ra138 (2016 Oct 19).","DOI":"10.1126\/scitranslmed.aag1711"},{"issue":"32","key":"52956_CR33","doi-asserted-by":"publisher","first-page":"13076","DOI":"10.1073\/pnas.1200419109","volume":"109","author":"M. Demers","year":"2012","unstructured":"Demers, M. et al. Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis. Proc Natl Acad Sci USA 2012 Aug 7; 109(32), 13076\u201381. Epub (2012 Jul 23).","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"52956_CR34","doi-asserted-by":"crossref","unstructured":"Fuchs, T. A. et al. Novel cell death program leads to neutrophil extracellular traps. J Cell Biol. 2007 Jan 15, 176(2), 231\u201341 (Epub 2007 Jan 8).","DOI":"10.1083\/jcb.200606027"},{"key":"52956_CR35","doi-asserted-by":"publisher","unstructured":"Nguyen, G. T., Green, E. R. & Mecsas, J. Neutrophils to the ROScue: Mechanisms of NADPH Oxidase Activation and Bacterial Resistance. Front Cell Infect Microbiol. 2017 Aug 25, 7 373, https:\/\/doi.org\/10.3389\/fcimb.2017.00373 eCollection (2017).","DOI":"10.3389\/fcimb.2017.00373"},{"key":"52956_CR36","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1002\/ijc.2910050303","volume":"5","author":"J Bubenik","year":"1970","unstructured":"Bubenik, J., Perlmann, P., Helmstein, K. & Moberger, G. Cellular and humoral immune responses tohuman urinary bladder carcinomas. Int J Cancer 5, 310\u2013319 (1970).","journal-title":"Int J Cancer"},{"key":"52956_CR37","first-page":"1986","volume":"30","author":"JJ Godleski","year":"1970","unstructured":"Godleski, J. J., Lee, R. E. & Leighton, J. Studies on the role of polymorphonuclear leukocytes in neoplastic disease with the chick embryo and Walker carcinosarcoma 256 in vivo and in vitro. Cancer Res 30, 1986\u20131993 (1970).","journal-title":"Cancer Res"},{"key":"52956_CR38","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1038\/newbio235186a0","volume":"235","author":"AH Pickaver","year":"1972","unstructured":"Pickaver, A. H., Ratcliffe, N. A., Williams, A. E. & Smiyh, H. Cytotoxic effects of peritoneal neutrophils on a syngenic rat tumour. Nat New Biol 235, 186\u2013187 (1972).","journal-title":"Nat New Biol"},{"issue":"1\u20134","key":"52956_CR39","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1002\/biof.5520240136","volume":"24","author":"M Zivkovic","year":"2005","unstructured":"Zivkovic, M. et al. Oxidative burst and anticancer activities of rat neutrophils. Biofactors. 24(1\u20134), 305\u201312 (2005).","journal-title":"Biofactors."},{"issue":"12","key":"52956_CR40","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1016\/j.imbio.2010.01.002","volume":"215","author":"Morana Jaganjac","year":"2010","unstructured":"Jaganjac, M et al. Granulocytes as effective anticancer agent in experimental solid tumor models. Immunobiology. 2010 Dec, 215(12), 1015 20, https:\/\/doi.org\/10.1016\/j.imbio.2010.01.002. Epub (2010 Jan 25).","journal-title":"Immunobiology"},{"issue":"18","key":"52956_CR41","doi-asserted-by":"publisher","first-page":"3160","DOI":"10.1182\/blood-2013-04-497446","volume":"122","author":"Marcello Albanesi","year":"2013","unstructured":"Albanesi, M. et al. Neutrophils mediate antibody-induced antitumor effects in mice. Blood. 2013 Oct 31, 122(18), 3160\u20134, https:\/\/doi.org\/10.1182\/blood-2013-04-497446 Epub (2013 Aug 26).","journal-title":"Blood"},{"issue":"1","key":"52956_CR42","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.canlet.2004.01.023","volume":"211","author":"Alessandra Soares Schanoski","year":"2004","unstructured":"Schanoski, A. S. et al. Walker 256 tumor MHC class I expression during the shift from A variant to the immunogenic AR variant. Cancer Lett., 211(1), 119\u201327 (2004 Jul 28).","journal-title":"Cancer Letters"},{"key":"52956_CR43","unstructured":"Kotteas, E. A. et al. The intercellular cell adhesion molecule-1 (icam-1) in lung cancer: implications for disease progression and prognosis. Anticancer Res, 34(9), 4665\u201372 (2014 Sep)."},{"key":"52956_CR44","doi-asserted-by":"crossref","unstructured":"H\u00e4nel, K. H., Cornelissen, C., L\u00fcscher, B. & Baron, J. M. Cytokines and the skin barrier. Int J Mol Sci, 14(4), 6720\u201345 (2013 Mar 26).","DOI":"10.3390\/ijms14046720"},{"key":"52956_CR45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.intimp.2016.02.007","volume":"34","author":"Keqiang Chen","year":"2016","unstructured":"Chen, K. et al. Tissue-resident dendritic cells and diseases involving dendritic cell malfunction. Int Immunopharmacol. (2016 May), 34, 1\u201315 (Epub 2016 Feb 22).","journal-title":"International Immunopharmacology"},{"key":"52956_CR46","doi-asserted-by":"crossref","unstructured":"Lyck, R. & Enzmann, G. The physiological roles of ICAM-1 and ICAM-2 in neutrophil migration into tissues. Curr Opin Hematol, 22(1), 53\u20139 (2015 Jan).","DOI":"10.1097\/MOH.0000000000000103"},{"key":"52956_CR47","doi-asserted-by":"crossref","unstructured":"Arnaout, M. A. Biology and structure of leukocyte \u03b2 2 integrins and their role in inflammation. F1000Res. 2016 Oct 4;5. eCollection (2016).","DOI":"10.12688\/f1000research.9415.1"},{"issue":"2","key":"52956_CR48","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1006\/bcmd.2002.0513","volume":"28","author":"M.Tarek Elghetany","year":"2002","unstructured":"Elghetany, M. T. Surface antigen changes during normal neutrophilic development: a critical review. Blood Cells Mol Dis., 28(2), 260\u201374 (2002 Mar-Apr).","journal-title":"Blood Cells, Molecules, and Diseases"},{"key":"52956_CR49","doi-asserted-by":"crossref","unstructured":"White-Owen, C., Alexander, J. W. & Babcock, G. F. Reduced expression of neutrophil CD11b and CD16 after severe traumatic injury. J Surg Res, 52(1), 22\u20136 (1992 Jan).","DOI":"10.1016\/0022-4804(92)90273-3"},{"issue":"1","key":"52956_CR50","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1038\/pr.2015.66","volume":"78","author":"Fiona M. O\u2019Hare","year":"2015","unstructured":"O\u2019Hare, F. M. et al. Neutrophil and monocyte toll-like receptor 4, CD11b and reactive oxygen intermediates, and neuroimaging outcomes in preterm infants. Pediatr Res. 2015 Jul, 78(1), 82\u201390 Epub (2015 Mar 31).","journal-title":"Pediatric Research"},{"key":"52956_CR51","doi-asserted-by":"publisher","first-page":"149185","DOI":"10.1155\/2014\/149185","volume":"2014","author":"G Landskron","year":"2014","unstructured":"Landskron, G., De la Fuente, M., Thuwajit, P., Thuwajit, C. & Hermoso, M. A. Chronic inflammation and cytokines in the tumor microenvironment. J Immunol Res. 2014, 149185 (2014).","journal-title":"J Immunol Res."},{"key":"52956_CR52","doi-asserted-by":"crossref","unstructured":"Coley, W. B. The treatment of malignant tumors by repeated inoculations of erysipelas. With a report of ten original cases. 1893. Clin Orthop Relat Res. 1991 Jan, 262, 3\u201311 (1893).","DOI":"10.1097\/00003086-199101000-00002"},{"key":"52956_CR53","unstructured":"Ardalan, M. R. Erysipelas-associated glomerulonephritis; a diagnostic puzzle. J Nephropharmacol. 2014 Jul 1, 3(2), 47\u201348 eCollection (2014)."},{"issue":"5","key":"52956_CR54","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1038\/jid.2009.437","volume":"130","author":"Adam Linder","year":"2010","unstructured":"Linder, A. et al. Erysipelas caused by group A streptococcus activates the contact system and induces the release of heparin-binding protein. J Invest Dermatol. 2010 May, 130(5), 1365\u201372. Epub (2010 Jan 28).","journal-title":"Journal of Investigative Dermatology"},{"key":"52956_CR55","doi-asserted-by":"crossref","unstructured":"Chicoine, M. R., Won, E. K. & Zahner, M. C. Intratumoral injection of lipopolysaccharide causes regression of subcutaneously implanted mouse glioblastoma multiforme. Neurosurgery. 48(3), 607\u201314; discussion 614\u20135 (2001 Mar).","DOI":"10.1097\/00006123-200103000-00032"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-52956-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-52956-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-52956-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T15:47:56Z","timestamp":1671292076000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-52956-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,11]]},"references-count":55,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["52956"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-52956-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,11]]},"assertion":[{"value":"15 April 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 October 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 November 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"16524"}}