{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:44:56Z","timestamp":1792788296940,"version":"4.5.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2015,7,2]],"date-time":"2015-07-02T00:00:00Z","timestamp":1435795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["#FS113028789"],"award-info":[{"award-number":["#FS113028789"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"name":"J.R.W."},{"name":"Arthritis Research-United Kingdom","award":["#19207."],"award-info":[{"award-number":["#19207."]}]},{"name":"A.W."},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["FS\/11\/19\/28761"],"award-info":[{"award-number":["FS\/11\/19\/28761"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Sexual dimorphisms exist in the incidence and severity of many diseases, with females demonstrating relative protection from inflammatory conditions. The extent and mechanisms by which excessive leukocyte recruitment underlies these differences are not well established, and better understanding is essential for the development of targeted therapies. Here, we set out to compare the male and female inflammatory response in a murine zymosan-induced peritonitis model and to understand how leukocyte subsets are mobilized from storage pools in both sexes. This work shows that female C57BL\/6 mice recruit fewer classical monocytes and neutrophils during zymosan-induced peritonitis. In addition, sex differences were evident in the circulation, as female mice showed reduced neutrophilia and monocytosis vs. male counterparts, despite having similar mobilization from BM stores. Importantly, we show that storage and trafficking of splenic leukocytes during acute inflammation are distinct between the sexes. Male mice have greater splenic stores of neutrophils and classical and nonclassical monocytes, despite similar spleen sizes, signifying another source of potential pathogenic leukocytes. This work demonstrates that males and females have distinct leukocyte-trafficking profiles in acute inflammation and suggests that the spleen, not the BM, plays a role in determining sex differences in the available pool of immune cells. Such dimorphisms demonstrate the importance of considering gender in assay development, drug design, and clinical trials.<\/jats:p>","DOI":"10.1189\/jlb.3a1214-601rr","type":"journal-article","created":{"date-parts":[[2015,7,3]],"date-time":"2015-07-03T10:50:32Z","timestamp":1435920632000},"page":"805-817","source":"Crossref","is-referenced-by-count":46,"title":["Sexual dimorphisms in leukocyte trafficking in a mouse peritonitis model"],"prefix":"10.1093","volume":"98","author":[{"given":"Emma","family":"Kay","sequence":"first","affiliation":[{"name":"William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Gomez-Garcia","sequence":"additional","affiliation":[{"name":"National Institute of Cardiology Ignacio Chavez , Mexico City , Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Woodfin","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramona S","family":"Scotland","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R","family":"Whiteford","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,7,2]]},"reference":[{"key":"2023013012475795500_B1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1385\/IR:34:3:177","article-title":"Sexual dimorphism in innate immune responses to infectious organisms","volume":"34","author":"Marriott","year":"2006","journal-title":"Immunol. Res."},{"key":"2023013012475795500_B2","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1172\/JCI200319429","article-title":"Sex is a potent modifier of the cardiovascular system","volume":"112","author":"Leinwand","year":"2003","journal-title":"J. Clin. Invest."},{"key":"2023013012475795500_B3","doi-asserted-by":"crossref","first-page":"5918","DOI":"10.1182\/blood-2011-03-340281","article-title":"Sex differences in resident immune cell phenotype underlie more efficient acute inflammatory responses in female mice","volume":"118","author":"Scotland","year":"2011","journal-title":"Blood"},{"key":"2023013012475795500_B4","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.4049\/jimmunol.0902866","article-title":"A new strategy for the identification of novel molecules with targeted proresolution of inflammation properties","volume":"184","author":"Navarro-Xavier","year":"2010","journal-title":"J. Immunol."},{"key":"2023013012475795500_B5","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1038\/sj.bjp.0701029","article-title":"Inhibition of neutrophil and monocyte recruitment by endogenous and exogenous lipocortin 1","volume":"120","author":"Getting","year":"1997","journal-title":"Br. J. Pharmacol."},{"key":"2023013012475795500_B6","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1007\/s00011-007-7131-1","article-title":"Role of lymphocytes in the course of murine zymosan-induced peritonitis","volume":"57","author":"Kolaczkowska","year":"2008","journal-title":"Inflamm. Res."},{"key":"2023013012475795500_B7","doi-asserted-by":"crossref","first-page":"4106","DOI":"10.1128\/MCB.20.11.4106-4114.2000","article-title":"Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion","volume":"20","author":"Jung","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"2023013012475795500_B8","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/S1550-8579(08)80007-1","article-title":"Pilot study of sex differences in chemokine\/cytokine markers of atherosclerosis in humans","volume":"5","author":"Leung","year":"2008","journal-title":"Gend. Med."},{"key":"2023013012475795500_B9","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1097\/01.CCM.0000266534.14262.E8","article-title":"Gender differences in the innate immune response and vascular reactivity following the administration of endotoxin to human volunteers","volume":"35","author":"Van Eijk","year":"2007","journal-title":"Crit. Care Med."},{"key":"2023013012475795500_B10","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1378\/chest.07-0420","article-title":"Influence of gender on the outcome of severe sepsis: a reappraisal","volume":"132","author":"Adrie","year":"2007","journal-title":"Chest"},{"key":"2023013012475795500_B11","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S1074-7613(03)00174-2","article-title":"Blood monocytes consist of two principal subsets with distinct migratory properties","volume":"19","author":"Geissmann","year":"2003","journal-title":"Immunity"},{"key":"2023013012475795500_B12","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1084\/jem.20021787","article-title":"Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2","volume":"197","author":"Gantner","year":"2003","journal-title":"J. Exp. Med."},{"key":"2023013012475795500_B13","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1189\/jlb.0807586","article-title":"Heterodimerization of TLR2 with TLR1 or TLR6 expands the ligand spectrum but does not lead to differential signaling","volume":"83","author":"Farhat","year":"2008","journal-title":"J. Leukoc. Biol."},{"key":"2023013012475795500_B14","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1124\/jpet.103.063776","article-title":"Critical role of L-selectin and histamine H4 receptor in zymosan-induced neutrophil recruitment from the bone marrow: comparison with carrageenan","volume":"310","author":"Takeshita","year":"2004","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2023013012475795500_B15","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/S1074-7613(00)80046-1","article-title":"The chemokine receptor CXCR4 is required for the retention of B lineage and granulocytic precursors within the bone marrow microenvironment","volume":"10","author":"Ma","year":"1999","journal-title":"Immunity"},{"key":"2023013012475795500_B16","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1126\/science.1175202","article-title":"Identification of splenic reservoir monocytes and their deployment to inflammatory sites","volume":"325","author":"Swirski","year":"2009","journal-title":"Science"},{"key":"2023013012475795500_B17","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1161\/CIRCULATIONAHA.111.061986","article-title":"Extramedullary hematopoiesis generates Ly-6C(high) monocytes that infiltrate atherosclerotic lesions","volume":"125","author":"Robbins","year":"2012","journal-title":"Circulation"},{"key":"2023013012475795500_B18","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1093\/eurheartj\/eht331","article-title":"Monocyte subset accumulation in the human heart following acute myocardial infarction and the role of the spleen as monocyte reservoir","volume":"35","author":"Van der Laan","year":"2014","journal-title":"Eur. Heart J."},{"key":"2023013012475795500_B19","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.expneurol.2013.05.002","article-title":"Mobilisation of the splenic monocyte reservoir and peripheral CXCR1 deficiency adversely affects recovery from spinal cord injury","volume":"247","author":"Blomster","year":"2013","journal-title":"Exp. Neurol."},{"key":"2023013012475795500_B20","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1056\/NEJM199802123380706","article-title":"Chemokines\u2014chemotactic cytokines that mediate inflammation","volume":"338","author":"Luster","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"2023013012475795500_B21","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/nri1964","article-title":"Tuning inflammation and immunity by chemokine sequestration: decoys and more","volume":"6","author":"Mantovani","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"2023013012475795500_B22","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1056\/NEJMra052723","article-title":"The many roles of chemokines and chemokine receptors in inflammation","volume":"354","author":"Charo","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"2023013012475795500_B23","doi-asserted-by":"crossref","first-page":"7341","DOI":"10.4049\/jimmunol.174.11.7341","article-title":"Proteolytic activation of alternative CCR1 ligands in inflammation","volume":"174","author":"Berahovich","year":"2005","journal-title":"J. Immunol."},{"key":"2023013012475795500_B24","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.1172\/JCI119798","article-title":"Impaired monocyte migration and reduced type 1 (Th1) cytokine responses in C-C chemokine receptor 2 knockout mice","volume":"100","author":"Boring","year":"1997","journal-title":"J. Clin. Invest."},{"key":"2023013012475795500_B25","doi-asserted-by":"crossref","first-page":"6846","DOI":"10.4049\/jimmunol.180.10.6846","article-title":"Additive roles for MCP-1 and MCP-3 in CCR2-mediated recruitment of inflammatory monocytes during Listeria monocytogenes infection","volume":"180","author":"Jia","year":"2008","journal-title":"J. Immunol."},{"key":"2023013012475795500_B26","doi-asserted-by":"crossref","first-page":"4308","DOI":"10.4049\/jimmunol.1301355","article-title":"Inflammatory responses induced by lipopolysaccharide are amplified in primary human monocytes but suppressed in macrophages by complement protein C5a","volume":"191","author":"Seow","year":"2013","journal-title":"J. Immunol."},{"key":"2023013012475795500_B27","doi-asserted-by":"crossref","first-page":"5616","DOI":"10.4049\/jimmunol.160.11.5616","article-title":"Novel C5a receptor antagonists regulate neutrophil functions in vitro and in vivo","volume":"160","author":"Pellas","year":"1998","journal-title":"J. Immunol."},{"key":"2023013012475795500_B28","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1182\/blood-2002-10-3228","article-title":"Rapid recruitment of inflammatory monocytes is independent of neutrophil migration","volume":"102","author":"Henderson","year":"2003","journal-title":"Blood"},{"key":"2023013012475795500_B29","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1097\/SHK.0b013e3182571e46","article-title":"Sex differences in inflammatory cytokines and CD99 expression following in vitro lipopolysaccharide stimulation","volume":"38","author":"Lef\u00e8vre","year":"2012","journal-title":"Shock"},{"key":"2023013012475795500_B30","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/nri2394","article-title":"The X-files in immunity: sex-based differences predispose immune responses","volume":"8","author":"Fish","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"2023013012475795500_B31","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/ni1309","article-title":"Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2","volume":"7","author":"Serbina","year":"2006","journal-title":"Nat. Immunol."},{"key":"2023013012475795500_B32","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/nri1669","article-title":"Structure and function of the spleen","volume":"5","author":"Mebius","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"2023013012475795500_B33","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/ni.2194","article-title":"B Cell-helper neutrophils stimulate the diversification and production of immunoglobulin in the marginal zone of the spleen","volume":"13","author":"Puga","year":"2012","journal-title":"Nat. Immunol."},{"key":"2023013012475795500_B34","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/nri3671","article-title":"Monocytes and macrophages: developmental pathways and tissue homeostasis","volume":"14","author":"Ginhoux","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"2023013012475795500_B35","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1126\/science.1178331","article-title":"Development of monocytes, macrophages, and dendritic cells","volume":"327","author":"Geissmann","year":"2010","journal-title":"Science"},{"key":"2023013012475795500_B36","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1002\/art.20309","article-title":"17 beta-Estradiol regulates cytokine release through modulation of CD16 expression in monocytes and monocyte-derived macrophages","volume":"50","author":"Kramer","year":"2004","journal-title":"Arthritis Rheum."},{"key":"2023013012475795500_B37","doi-asserted-by":"crossref","first-page":"3877","DOI":"10.1210\/en.2009-0098","article-title":"Estrogens augment cell surface TLR4 expression on murine macrophages and regulate sepsis susceptibility in vivo","volume":"150","author":"Rettew","year":"2009","journal-title":"Endocrinology"},{"key":"2023013012475795500_B38","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1161\/ATVBAHA.111.223545","article-title":"Suppression of endothelial P-selectin expression contributes to reduced cell trafficking in females: an effect independent of NO and prostacyclin","volume":"31","author":"Villar","year":"2011","journal-title":"Arterioscler. Thromb. Vasc. Biol."}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/98\/5\/805\/48174742\/jlb0805.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/98\/5\/805\/48174742\/jlb0805.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T08:33:23Z","timestamp":1677486803000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/98\/5\/805\/6935866"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,2]]},"references-count":38,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2015,7,2]]},"published-print":{"date-parts":[[2015,11,1]]}},"URL":"https:\/\/doi.org\/10.1189\/jlb.3a1214-601rr","relation":{},"ISSN":["0741-5400","1938-3673"],"issn-type":[{"value":"0741-5400","type":"print"},{"value":"1938-3673","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2015,11]]},"published":{"date-parts":[[2015,7,2]]}}}