{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T05:21:10Z","timestamp":1773292870780,"version":"3.50.1"},"reference-count":45,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2006,5,15]]},"abstract":"<jats:p>In cell suspensions subjected to high-shear rotatory motion, human PMN (polymorphonuclear cells) adhered to E-selectin-expressing CHO (Chinese-hamster ovary) cells (CHO-E), and formed homotypic aggregates when challenged by E-selectin\u2013IgG fusion protein, by a mechanism that involved \u03b22 integrins. Both heterotypic and homotypic PMN adhesion was accompanied by tyrosine phosphorylation of a 110\u00a0kDa protein (P110). This event was prevented by blocking anti-(\u03b22 integrin) antibodies and by inhibitors of Src-family kinases, suggesting that it was part of an \u2018outside-in\u2019 signalling that was initiated by integrin engagement. Interestingly, Src-family kinase inhibitors prevented \u03b22-integrin-mediated (i) homotypic PMN adhesion triggered by E-selectin\u2013IgG, (ii) heterotypic CHO-E\/PMN adhesion in mixed-cell suspensions, and (iii) firm adhesion of PMN to CHO-E monolayers under physiological flow. Similarly to PMN treated with Src-family kinase inhibitors, PMN from hck\u2212\/\u2212fgr\u2212\/\u2212 and hck\u2212\/\u2212fgr\u2212\/\u2212lyn\u2212\/\u2212 mice showed significant impairment of \u03b22-integrin-mediated adhesion to CHO-E. Moreover, the expression of \u03b22 integrin activation epitopes at the sites of cell\u2013cell contact in CHO-E\/PMN conjugates was abolished by Src-family kinase inhibitors. One component of P110 was identified as the FAK (focal adhesion kinase) Pyk2 (proline-rich tyrosine kinase 2), which was phosphorylated in a \u03b22 integrin- and Src-family-kinase-dependent manner. Thus, Src-family kinases, and perhaps Pyk2, mediate a signal necessary for \u03b22 integrin function in PMN tethered by E-selectin.<\/jats:p>","DOI":"10.1042\/bj20051924","type":"journal-article","created":{"date-parts":[[2006,4,28]],"date-time":"2006-04-28T18:24:37Z","timestamp":1146248677000},"page":"89-98","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Src-family kinases mediate an outside-in signal necessary for \u03b22 integrins to achieve full activation and sustain firm adhesion of polymorphonuclear leucocytes tethered on E-selectin"],"prefix":"10.1042","volume":"396","author":[{"given":"Licia","family":"Totani","sequence":"first","affiliation":[{"name":"Laboratory of Vascular Biology and Pharmacology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Piccoli","sequence":"additional","affiliation":[{"name":"Laboratory of Vascular Biology and Pharmacology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Manarini","sequence":"additional","affiliation":[{"name":"Laboratory of Vascular Biology and Pharmacology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Federico","sequence":"additional","affiliation":[{"name":"Laboratory of Vascular Biology and Pharmacology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Romina","family":"Pecce","sequence":"additional","affiliation":[{"name":"Laboratory of Vascular Biology and Pharmacology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Martelli","sequence":"additional","affiliation":[{"name":"Laboratory of Vascular Biology and Pharmacology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Cerletti","sequence":"additional","affiliation":[{"name":"Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso 86100, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Piccardoni","sequence":"additional","affiliation":[{"name":"Laboratory of Vascular Biology and Pharmacology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clifford\u00a0A.","family":"Lowell","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of California, San Francisco 94143, CA, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan\u00a0S.","family":"Smyth","sequence":"additional","affiliation":[{"name":"North Carolina Cardiovascular Biology Center, Department of Medicine, The University of North Carolina, Chapel Hill, NC, 27599-7126, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgio","family":"Berton","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section of General Pathology, University of Verona, Verona 37134, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virgilio","family":"Evangelista","sequence":"additional","affiliation":[{"name":"Laboratory of Vascular Biology and Pharmacology, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2006,4,26]]},"reference":[{"key":"2021112213053222600_B1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1034\/j.1600-065X.2002.18602.x","article-title":"Integration of inflammatory signals by rolling neutrophils","volume":"186","author":"Ley","year":"2002","journal-title":"Immunol. 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