{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T22:16:55Z","timestamp":1780093015526,"version":"3.54.0"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>A2A adenosine receptor (A2AAR) signaling negatively regulates inflammatory responses in many disease models, but the detailed mechanisms remain unclear. We used the selective A2AAR agonist, ATL313, to examine how A2AAR signaling affects human and murine neutrophil adhesion under flow. Treating neutrophils with ATL313 inhibited selectin-induced, \u03b22 integrin\u2013dependent slow rolling and chemokine-induced, \u03b22 integrin\u2013dependent arrest on ICAM-1. ATL313 inhibited selectin-induced \u03b22 integrin extension, which supports slow rolling, and chemokine-induced hybrid domain \u201cswing-out,\u201d which supports arrest. Furthermore, ATL313 inhibited integrin outside-in signaling as revealed by reduced neutrophil superoxide production and spreading on immobilized anti\u2013\u03b22 integrin Ab. ATL313 suppressed selectin-triggered activation of Src family kinases (SFKs) and p38 MAPK, chemokine-triggered activation of Ras-related protein 1, and \u03b22 integrin\u2013triggered activation of SFKs and Vav cytoskeletal regulatory proteins. ATL313 activated protein kinase A and its substrate C-terminal Src kinase, an inhibitor of SFKs. Treating neutrophils with a protein kinase A inhibitor blocked the actions of ATL313. In vivo, ATL313-treated neutrophils rolled faster and arrested much less frequently in postcapillary venules of the murine cremaster muscle after TNF-\u03b1 challenge. Furthermore, ATL313 markedly suppressed neutrophil migration into the peritoneum challenged with thioglycollate. ATL313 did not affect A2AAR-deficient neutrophils, confirming its specificity. Our findings provide new insights into the anti-inflammatory mechanisms of A2AAR signaling and the potential utility of A2AAR agonists in inflammatory diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.1500775","type":"journal-article","created":{"date-parts":[[2015,9,10]],"date-time":"2015-09-10T13:40:10Z","timestamp":1441892410000},"page":"3880-3889","source":"Crossref","is-referenced-by-count":39,"title":["Multi-Inhibitory Effects of A2A Adenosine Receptor Signaling on Neutrophil Adhesion Under Flow"],"prefix":"10.1093","volume":"195","author":[{"given":"Tadayuki","family":"Yago","sequence":"first","affiliation":[{"name":"Cardiovascular Biology Program, Oklahoma Medical Research Foundation , Oklahoma City, OK 73104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Tsukamoto","sequence":"additional","affiliation":[{"name":"Immunobiology and Cancer Program, Oklahoma Medical Research Foundation , Oklahoma City, OK 73104"},{"name":"Laboratory of Oncology, Pharmacy Practice and Sciences, Graduate School of Pharmaceutical Sciences, Tohoku University , Sendai 980-8578 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenghui","family":"Liu","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Program, Oklahoma Medical Research Foundation , Oklahoma City, OK 73104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Program, Oklahoma Medical Research Foundation , Oklahoma City, OK 73104"},{"name":"Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center , Oklahoma City, OK 73104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda F","family":"Thompson","sequence":"additional","affiliation":[{"name":"Immunobiology and Cancer Program, Oklahoma Medical Research Foundation , Oklahoma City, OK 73104"},{"name":"Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center , Oklahoma City, OK 73104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodger P","family":"McEver","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Program, Oklahoma Medical Research Foundation , Oklahoma City, OK 73104"},{"name":"Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center , Oklahoma City, OK 73104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,10,15]]},"reference":[{"key":"2025030704174571600_r1","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/nrd2638","article-title":"Adenosine receptors: therapeutic aspects for inflammatory and immune diseases","volume":"7","author":"Hask\u00f3","year":"2008","journal-title":"Nat. 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