{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:46:29Z","timestamp":1781106389284,"version":"3.54.1"},"reference-count":84,"publisher":"National Academy of Sciences","issue":"10","license":[{"start":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T00:00:00Z","timestamp":1614729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM32373"],"award-info":[{"award-number":["R01GM32373"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2021,3,9]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Sepsis is a condition wherein a microbial infection leads to life-threatening systemic hyperactivation of innate immunity. Blood pH is normally maintained tightly between 7.35 and 7.45, and lactic acidosis with a pH &lt;7.3 indicates a poor prognosis in sepsis, also associated with low zinc levels. Release of HMGB1 from activated and\/or necrotic tissues plays a pivotal role in triggering the proinflammatory cascade of late sepsis. Using an in vitro whole-blood assay, we observed that HMGB1 cannot mediate proinflammatory activity at physiological pH and zinc concentrations. This is due to zinc-dependent association of HMGB1 with sialoglycoproteins, thereby preventing its binding with proinflammatory receptors. Thus, a drop in pH and zinc concentration in sepsis can release sequestered HMGB1 and trigger the inflammatory cascade.<\/jats:p>","DOI":"10.1073\/pnas.2018090118","type":"journal-article","created":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T20:05:21Z","timestamp":1614801921000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":16,"title":["Sialoglycan recognition is a common connection linking acidosis, zinc, and HMGB1 in sepsis"],"prefix":"10.1073","volume":"118","author":[{"given":"Shoib S.","family":"Siddiqui","sequence":"first","affiliation":[{"name":"Department of Medicine, University of California San Diego, La Jolla, CA 92093;"},{"name":"Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093;"},{"name":"Glycobiology Research and Training Center, University of California San Diego, La Jolla, CA 92093;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7351-485X","authenticated-orcid":false,"given":"Chirag","family":"Dhar","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego, La Jolla, CA 92093;"},{"name":"Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093;"},{"name":"Glycobiology Research and Training Center, University of California San Diego, La Jolla, CA 92093;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9245-1604","authenticated-orcid":false,"given":"Venkatasubramaniam","family":"Sundaramurthy","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego, La Jolla, CA 92093;"},{"name":"Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093;"},{"name":"Glycobiology Research and Training Center, University of California San Diego, La Jolla, CA 92093;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5446-8192","authenticated-orcid":false,"given":"Aniruddha","family":"Sasmal","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego, La Jolla, CA 92093;"},{"name":"Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093;"},{"name":"Glycobiology Research and Training Center, University of California San Diego, La Jolla, CA 92093;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4378-0532","authenticated-orcid":false,"given":"Hai","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of California, Davis, CA 95616;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3875-8872","authenticated-orcid":false,"given":"Esther","family":"Bandala-Sanchez","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia;"},{"name":"Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4508-196X","authenticated-orcid":false,"given":"Miaomiao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, School of Dental Medicine, University at Buffalo, The State University of New York, Buffalo, NY 14214"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1321-0798","authenticated-orcid":false,"given":"Xiaoxiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, School of Dental Medicine, University at Buffalo, The State University of New York, Buffalo, NY 14214"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3160-614X","authenticated-orcid":false,"given":"Xi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of California, Davis, CA 95616;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2500-8944","authenticated-orcid":false,"given":"Leonard C.","family":"Harrison","sequence":"additional","affiliation":[{"name":"The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia;"},{"name":"Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9380-2712","authenticated-orcid":false,"given":"Ding","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, School of Dental Medicine, University at Buffalo, The State University of New York, Buffalo, NY 14214"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2206-975X","authenticated-orcid":false,"given":"Ajit","family":"Varki","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego, La Jolla, CA 92093;"},{"name":"Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093;"},{"name":"Glycobiology Research and Training Center, University of California San Diego, La Jolla, CA 92093;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2021,3,3]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.07400715"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30566-3"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1309483"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-014-0503-3"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/642462"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcrc.2011.05.025"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2402"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.36"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01446"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2014.863876"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2010.02.021"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.4.565"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-0492-x"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-11-751636"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200318882"},{"key":"e_1_3_4_16_2","volume-title":"Merck Manual: Professional Edition","author":"Maggio P. M.","year":"2003","unstructured":"P. M. Maggio, \u201cSepsis and septic shock\u201d in Merck Manual: Professional Edition, M. H. Beers, A. J. Fletcher, Eds. (Merck Research Laboratories, Whitehouse Station, NJ, 2003)."},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.4110\/in.2018.18.e27"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0215-7"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R114.619304"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2014.07.025"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5425.248"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.shk.0000225404.51320.82"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1003893107"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132603"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1168988"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1722056115"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2362.1999.00485.x"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2199-9-32"},{"key":"e_1_3_4_29_2","first-page":"1041","article-title":"[The structure of the complexes of DNA with non-histone chromosomal protein HMGB1 in the presence of manganese ions]","volume":"38","author":"Polianichko A. M.","year":"2004","unstructured":"A. M. Polianichko, E. V. Chikhirzhina, E. I. Kostyleva, V. I. Vorob\u2019ev, [The structure of the complexes of DNA with non-histone chromosomal protein HMGB1 in the presence of manganese ions]. Mol. Biol. (Mosk.) 38, 1041\u20131049 (2004).","journal-title":"Mol. Biol. (Mosk.)"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh242"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01967"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.274217"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-4102"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.359323"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.299685"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aav8075"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1973.tb03026.x"},{"key":"e_1_3_4_38_2","first-page":"101","article-title":"Emerging roles for HMGB1 protein in immunity, inflammation, and cancer","volume":"4","author":"Martinotti S.","year":"2015","unstructured":"S. Martinotti, M. Patrone, E. Ranzato, Emerging roles for HMGB1 protein in immunity, inflammation, and cancer. ImmunoTargets Ther. 4, 101\u2013109 (2015).","journal-title":"ImmunoTargets Ther."},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2014.05.001"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108417200"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2016.06.031"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2006.08.034"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature00858"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.12.040194.005015"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg516"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1212662"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399408000884"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2434651100"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.85375"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-05-719757"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2376"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2610"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.226258"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2008.107821"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.6.4037"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20120189"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2015.6409"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12601"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2015.03.008"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1177\/15648265070283S303"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2017.173"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4838(00)00153-9"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2007.10.004"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwh034"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/9.10.1003"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006087"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2017.12.002"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0176069"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aev073"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00179.2015"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0502257102"},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2016.07.008"},{"key":"e_1_3_4_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32989-7"},{"key":"e_1_3_4_74_2","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12106"},{"key":"e_1_3_4_75_2","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2019.11.81"},{"key":"e_1_3_4_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2004.01.037"},{"key":"e_1_3_4_77_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-020-00172-4"},{"key":"e_1_3_4_78_2","doi-asserted-by":"publisher","DOI":"10.1159\/000508291"},{"key":"e_1_3_4_79_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-020-06022-5"},{"key":"e_1_3_4_80_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.4783"},{"key":"e_1_3_4_81_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006461"},{"key":"e_1_3_4_82_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00113811"},{"key":"e_1_3_4_83_2","doi-asserted-by":"publisher","DOI":"10.1364\/OE.23.027724"},{"key":"e_1_3_4_84_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-015-1341-8"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.2018090118","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2018090118","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T06:49:01Z","timestamp":1649832541000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2018090118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,3]]},"references-count":84,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,3,9]]}},"alternative-id":["10.1073\/pnas.2018090118"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2018090118","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.07.15.198010","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,3]]},"assertion":[{"value":"2021-03-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2018090118"}}