{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T01:04:05Z","timestamp":1776042245084,"version":"3.50.1"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,5,17]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Lung injury, a severe adverse outcome of lipopolysaccharide\u2010induced acute respiratory distress syndrome, is attributed to excessive neutrophil recruitment and effector response. Poldip2 (polymerase \u03b4\u2010interacting protein 2) plays a critical role in regulating endothelial permeability and leukocyte recruitment in acute inflammation. Thus, we hypothesized that\n              <jats:italic>myeloid<\/jats:italic>\n              Poldip2 is involved in neutrophil recruitment to inflamed lungs.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              After characterizing myeloid\u2010specific\n              <jats:italic>Poldip2<\/jats:italic>\n              knockout mice, we showed that at 18\u00a0hours post\u2010lipopolysaccharide injection, bronchoalveolar lavage from myeloid Poldip2\u2010deficient mice contained fewer inflammatory cells (8 [4\u201316] versus 29 [12\u201357]\u00d710\n              <jats:sup>4<\/jats:sup>\n              \/mL in wild\u2010type mice) and a smaller percentage of neutrophils (30% [28%\u201334%] versus 38% [33%\u201341%] in wild\u2010type mice), while the main chemoattractants for neutrophils remained unaffected. In vitro, Poldip2\u2010deficient neutrophils responded as well as wild\u2010type neutrophils to inflammatory stimuli with respect to neutrophil extracellular trap formation, reactive oxygen species production, and induction of cytokines. However, neutrophil adherence to a tumor necrosis factor\u2010\u03b1 stimulated endothelial monolayer was inhibited by Poldip2 depletion (225 [115\u2013272] wild\u2010type [myePoldip2\n              <jats:sup>+\/+<\/jats:sup>\n              ] versus 133 [62\u2013178] myeloid\u2010specific\n              <jats:italic>Poldip2<\/jats:italic>\n              knockout [myePoldip2\n              <jats:sup>\u2010\/\u2010<\/jats:sup>\n              ] neutrophils) as was transmigration (1.7 [1.3\u20132.1] versus 1.1 [1.0\u20131.4] relative to baseline transmigration). To determine the underlying mechanism, we examined the surface expression of \u03b22\u2010integrin, its binding to soluble intercellular adhesion molecule 1, and Pyk2 phosphorylation. Surface expression of \u03b22\u2010integrins was not affected by Poldip2 deletion, whereas \u03b22\u2010integrins and Pyk2 were less activated in Poldip2\u2010deficient neutrophils.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">These results suggest that myeloid Poldip2 is involved in \u03b22\u2010integrin activation during the inflammatory response, which in turn mediates neutrophil\u2010to\u2010endothelium adhesion in lipopolysaccharide\u2010induced acute respiratory distress syndrome.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.025181","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T09:03:50Z","timestamp":1652173430000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Myeloid Poldip2 Contributes to the Development of Pulmonary Inflammation by Regulating Neutrophil Adhesion in a Murine Model of Acute Respiratory Distress Syndrome"],"prefix":"10.1161","volume":"11","author":[{"given":"Ziwei","family":"Ou","sequence":"first","affiliation":[{"name":"Division of Cardiology Department of Medicine Emory University Atlanta GA"},{"name":"Department of Cardiovascular Medicine Xiangya HospitalCentral South University Changsha China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Dolmatova","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medicine Emory University Atlanta GA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9240-5368","authenticated-orcid":false,"given":"Rohan","family":"Mandavilli","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medicine Emory University Atlanta GA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyan","family":"Qu","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medicine Emory University Atlanta GA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgette","family":"Gafford","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medicine Emory University Atlanta GA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taylor","family":"White","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medicine Emory University Atlanta GA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandra","family":"Valdivia","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medicine Emory University Atlanta GA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernard","family":"Lass\u00e8gue","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medicine Emory University Atlanta GA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6238-1441","authenticated-orcid":false,"given":"Marina S.","family":"Hernandes","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medicine Emory University Atlanta GA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9456-8582","authenticated-orcid":false,"given":"Kathy K.","family":"Griendling","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medicine Emory University Atlanta GA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0069-0"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.4103\/0974-2700.58663"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.21907"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1608077"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2017.12.18"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2010.00138"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3024"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.157.10.4609"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.4694"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00031-20"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.148.6.1847"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1628"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M208694200"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M414597200"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00918.2013"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.193722"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2016.03.001"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1720693115"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.113.301913"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-84987-z"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20180944"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096657"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0247261"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-8570-8_20"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.3791\/53936-v"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-08-373118"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.3VMA0918-374R"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(02)53050-0"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012355"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btn227"},{"key":"e_1_3_2_32_2","volume-title":"R: A language and environment for statistical computing","author":"R Core Team","year":"2018","unstructured":"R Core Team . R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2018."},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01259"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2015.07.007"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-020712-164023"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.09.018"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2007.05.017"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(03)00117-0"},{"key":"e_1_3_2_39_2","article-title":"Quantitative in vitro assay to measure neutrophil adhesion to activated primary human microvascular endothelial cells under static conditions","author":"Wilhelmsen K","year":"2013","unstructured":"Wilhelmsen K, Farrar K, Hellman J. Quantitative in vitro assay to measure neutrophil adhesion to activated primary human microvascular endothelial cells under static conditions. J Vis Exp. 2013:e50677. doi: 10.3791\/50677","journal-title":"J Vis Exp"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)00539-6"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.5.1733"},{"key":"e_1_3_2_42_2","first-page":"490","article-title":"Chemotactic activity in bronchoalveolar lavage fluid from patients with adult respiratory distress syndrome","volume":"132","author":"Parsons PE","year":"1985","unstructured":"Parsons PE, Fowler AA, Hyers TM, Henson PM. Chemotactic activity in bronchoalveolar lavage fluid from patients with adult respiratory distress syndrome. Am Rev Respir Dis. 1985;132:490\u2013493.","journal-title":"Am Rev Respir Dis"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.150.1.8025736"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.2000.279.6.L1137"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/817038"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V100.12.3853"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.193.7.863"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.127.6.1617"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-01-0303"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4644(19960616)61:4<554::AID-JCB8>3.0.CO;2-N"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1086652"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1722"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0802984"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2016.01.016"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.121.025181","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:06:40Z","timestamp":1715598400000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.121.025181"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,17]]},"references-count":53,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,5,17]]}},"alternative-id":["10.1161\/JAHA.121.025181"],"URL":"https:\/\/doi.org\/10.1161\/jaha.121.025181","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,17]]},"assertion":[{"value":"2021-12-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e025181"}}