{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T11:41:47Z","timestamp":1789904507667,"version":"4.0.1"},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,2,8]],"date-time":"2018-02-08T00:00:00Z","timestamp":1518048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["FS\/10\/73\/28464"],"award-info":[{"award-number":["FS\/10\/73\/28464"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G0802001"],"award-info":[{"award-number":["G0802001"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Neutrophils are key components of the innate immune response, providing host defence against infection and being recruited to non\u2010microbial injury sites. Platelets act as a trigger for neutrophil extravasation to inflammatory sites but mechanisms and tissue\u2010specific aspects of these interactions are currently unclear. Here, we use bacterial endotoxin in mice to trigger an innate inflammatory response in different tissues and measure neutrophil invasion with or without platelet reduction. We show that platelets are essential for neutrophil infiltration to the brain, peritoneum and skin. Neutrophil numbers do not rise above basal levels in the peritoneum and skin and are decreased (~60%) in the brain when platelet numbers are reduced. In contrast neutrophil infiltration in the lung is unaffected by platelet reduction, up\u2010regulation of <jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>\u20101 (2\u00b74\u2010fold) and <jats:styled-content style=\"fixed-case\">CCL<\/jats:styled-content>5 (1\u00b74\u2010fold) acting as a compensatory mechanism in platelet\u2010reduced mice during lung inflammation. In brain inflammation targeting platelet receptor GPIb<jats:italic>\u03b1<\/jats:italic> results in a significant decrease (44%) in platelet\u2010mediated neutrophil invasion, while maintaining platelet numbers in the circulation. These results suggest that therapeutic blockade of platelet GPIb<jats:italic>\u03b1<\/jats:italic> could limit the harmful effects of excessive inflammation while minimizing haemorrhagic complications of platelet reduction in the brain. The data also demonstrate the ability to target damaging brain inflammation in stroke and related disorders without compromising lung immunity and hence risk of pneumonia, a major complication post stroke. In summary, our data reveal an important role for platelets in neutrophil infiltration to various tissues, including the brain, and so implicate platelets as a key, targetable component of cerebrovascular inflammatory disease or injury.<\/jats:p>","DOI":"10.1111\/imm.12892","type":"journal-article","created":{"date-parts":[[2018,1,12]],"date-time":"2018-01-12T00:17:08Z","timestamp":1515716228000},"page":"322-328","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Neutrophil infiltration to the brain is platelet\u2010dependent, and is reversed by blockade of platelet GPIb<i>\u03b1<\/i>"],"prefix":"10.1111","volume":"154","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3197-3062","authenticated-orcid":false,"given":"James A.","family":"Giles","sequence":"first","affiliation":[{"name":"Faculty of Biology, Medicine and Health University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4766-2293","authenticated-orcid":false,"given":"Andrew D.","family":"Greenhalgh","sequence":"additional","affiliation":[{"name":"Centre for Research in Neuroscience Montreal General Hospital McGill University Health Centre Montreal QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Denes","sequence":"additional","affiliation":[{"name":"\u201cMomentum\u201d Laboratory of Neuroimmunology Institute of Experimental Medicine Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Nieswandt","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine University Hospital and Rudolf Virchow Centre for Experimental Biomedicine University of W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham","family":"Coutts","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry W.","family":"McColl","sequence":"additional","affiliation":[{"name":"The Roslin Institute &amp; R(D)SVS University of Edinburgh Easter Bush, Midlothian UK"},{"name":"Edinburgh Medical School UK Dementia Research Institute at The University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart M.","family":"Allan","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,2,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-030409-101311"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2007.06.009"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1256478"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2013.06.004"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1998.6785"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5376-06.2007"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1109766"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1400401"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201444748"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2012.98"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2014.04.023"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1206758"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3399"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.691279"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-014-1355-2"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0303510101"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1200409"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24146"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3109\/09537101003695339"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-11-252643"}],"container-title":["Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fimm.12892","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imm.12892","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T11:30:53Z","timestamp":1694691053000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imm.12892"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,8]]},"references-count":20,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["10.1111\/imm.12892"],"URL":"https:\/\/doi.org\/10.1111\/imm.12892","archive":["Portico"],"relation":{},"ISSN":["0019-2805","1365-2567"],"issn-type":[{"value":"0019-2805","type":"print"},{"value":"1365-2567","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,8]]},"assertion":[{"value":"2017-07-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-12-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-02-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}