{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T10:23:16Z","timestamp":1770286996754,"version":"3.49.0"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,1,23]],"date-time":"2018-01-23T00:00:00Z","timestamp":1516665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007150","name":"United Therapeutics Corporation","doi-asserted-by":"publisher","award":["U19 AI090959"],"award-info":[{"award-number":["U19 AI090959"]}],"id":[{"id":"10.13039\/100007150","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007150","name":"United Therapeutics Corporation","doi-asserted-by":"publisher","award":["P01 HL107152"],"award-info":[{"award-number":["P01 HL107152"]}],"id":[{"id":"10.13039\/100007150","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008510","name":"University of Maryland","doi-asserted-by":"publisher","award":["2T32HL007698\u201022A1"],"award-info":[{"award-number":["2T32HL007698\u201022A1"]}],"id":[{"id":"10.13039\/100008510","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Alongside the need to develop more effective and less toxic immunosuppression, the shortage of human organs available for organ transplantation is one of the major hurdles facing the field. Research into xenotransplantation, as an alternative source of organs, has unveiled formidable challenges. Porcine lungs perfused with human blood rapidly sequester the majority of circulating neutrophils and platelets, which leads to inflammation and organ failure within hours, and is not significantly attenuated by genetic modifications to the pig targeted to diminish antibody binding and complement and coagulation cascade activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we model the interaction of freshly isolated human leukocytes with xenotransplanted vasculature under physiologic flow conditions using microfluidic channels coated with porcine endothelial cells. Both isolated human neutrophils and whole human blood were perfused over transgenic pig aortic endothelial cells that had been activated with rhTNF\u2010\u03b1 or rhIL\u20104 using the BioFlux system. Novel compounds GMI\u20101271 and rPSGL1.Fc were tested as E\u2010 and P\u2010 selectin antagonists, respectively. Cellular adhesion and rolling events were tracked using FIJI (imageJ).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Porcine endothelium activated with either rhTNF\u2010\u03b1 or rhIL\u20104 expressed high amounts of selectins, to which isolated human neutrophils readily rolled and tethered. Both E\u2010and P\u2010selectin antagonism significantly reduced the number of neutrophils rolling and rolling distance in a dose\u2010dependent manner, with near total inhibition at higher doses (<jats:italic>P<\/jats:italic>&lt; .001). Similarly, with whole human blood, selectin blocking compounds exhibited dose\u2010dependent inhibition of prevalent leukocyte adhesion and severe endothelial injury (Untreated: 394 \u00b1 97 PMNs\/hpf, 57 \u00b1 6% loss EC; GMI1271+rPSGL1.Fc: 23 \u00b1 9 PMNs\/hpf, 8 \u00b1 6% loss EC<jats:italic>P<\/jats:italic>&lt; .01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Selectin blockade may be useful as part of an integrated strategy to prevent neutrophil\u2010mediated organ xenograft injury, especially during the early time points following reperfusion.<\/jats:p><\/jats:sec>","DOI":"10.1111\/xen.12381","type":"journal-article","created":{"date-parts":[[2018,1,23]],"date-time":"2018-01-23T07:02:45Z","timestamp":1516690965000},"source":"Crossref","is-referenced-by-count":22,"title":["P\u2010 and E\u2010selectin receptor antagonism prevents human leukocyte adhesion to activated porcine endothelial monolayers and attenuates porcine endothelial damage"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0733-8720","authenticated-orcid":false,"given":"Christopher T.","family":"Laird","sequence":"first","affiliation":[{"name":"University of Maryland SOM Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wessam","family":"Hassanein","sequence":"additional","affiliation":[{"name":"University of Maryland SOM Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4762-3400","authenticated-orcid":false,"given":"Natalie A.","family":"O'Neill","sequence":"additional","affiliation":[{"name":"University of Maryland SOM Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6493-318X","authenticated-orcid":false,"given":"Beth M.","family":"French","sequence":"additional","affiliation":[{"name":"University of Maryland SOM Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangfei","family":"Cheng","sequence":"additional","affiliation":[{"name":"University of Maryland SOM Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William E.","family":"Fogler","sequence":"additional","affiliation":[{"name":"GlycoMimetics, Inc Rockville MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John L.","family":"Magnani","sequence":"additional","affiliation":[{"name":"GlycoMimetics, Inc Rockville MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dawn","family":"Parsell","sequence":"additional","affiliation":[{"name":"University of Maryland SOM Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8179-2569","authenticated-orcid":false,"given":"Arielle","family":"Cimeno","sequence":"additional","affiliation":[{"name":"University of Maryland SOM Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol J.","family":"Phelps","sequence":"additional","affiliation":[{"name":"Revivicor, Inc Blacksburg VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Ayares","sequence":"additional","affiliation":[{"name":"Revivicor, Inc Blacksburg VA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Burdorf","sequence":"additional","affiliation":[{"name":"University of Maryland SOM Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnes M.","family":"Azimzadeh","sequence":"additional","affiliation":[{"name":"University of Maryland SOM Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"III","given":"Richard N.","family":"Pierson","sequence":"additional","affiliation":[{"name":"University of Maryland SOM Baltimore MD USA"},{"name":"GlycoMimetics, Inc Rockville MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,1,23]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"HigginbothamL KimS MathewsD.Late renal xenograft failure is antibody\u2010mediated: description of the longest\u2010reported survival in pig\u2010to\u2010primate renal xenotransplantation.2016American Transplant Congress. 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