{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T05:51:46Z","timestamp":1761630706902},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,12,22]],"date-time":"2014-12-22T00:00:00Z","timestamp":1419206400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Health and Medical Research Council of Australia"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Experimental Path"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Kidney allografts induce strong <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\u2010cell and antibody responses which mediate acute rejection. Spleen tyrosine kinase (<jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>yk) is expressed by most leucocytes, except mature <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content> cells, and is involved in intracellular signalling following activation of the <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>c\u03b3\u2010receptor, <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>\u2010cell receptor and some integrins. A role for <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>yk signalling has been established in antibody\u2010dependent native kidney disease, but little is known of <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>yk in acute renal allograft rejection. Sprague\u2013<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>awley rats underwent bilateral nephrectomy and received an orthotopic <jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>istar renal allograft. Recipient rats were treated with a <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>yk inhibitor (<jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>0482417, 30\u00a0mg\/kg\/bid), or vehicle, from 1\u00a0h before surgery until being killed 5\u00a0days later. Vehicle\u2010treated recipients developed severe allograft failure with marked histologic damage in association with dense leucocyte infiltration (<jats:styled-content style=\"fixed-case\">T<\/jats:styled-content> cells, macrophages, neutrophils and <jats:styled-content style=\"fixed-case\">NK<\/jats:styled-content> cells) and deposition of <jats:styled-content style=\"fixed-case\">I<\/jats:styled-content>g<jats:styled-content style=\"fixed-case\">M<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> I<\/jats:styled-content>g<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>3. Immunostaining identified <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>yk expression by many infiltrating leucocytes. <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>0482417 treatment significantly improved allograft function and reduced histologic damage, although allograft injury was still clearly evident. <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>0482417 failed to prevent <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\u2010cell infiltration and activation within the allograft. However, <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>0482417 significantly attenuated acute tubular necrosis, infiltration of macrophages and neutrophils and thrombosis of peritubular capillaries. In conclusion, this study identifies a role for <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>yk in acute renal allograft rejection. <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>yk inhibition may be a useful addition to <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\u2010cell\u2010based immunotherapy in renal transplantation.<\/jats:p>","DOI":"10.1111\/iep.12110","type":"journal-article","created":{"date-parts":[[2014,12,22]],"date-time":"2014-12-22T07:59:56Z","timestamp":1419235196000},"page":"54-62","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Spleen tyrosine kinase contributes to acute renal allograft rejection in the rat"],"prefix":"10.1111","volume":"96","author":[{"given":"Sharmila","family":"Ramessur Chandran","sequence":"first","affiliation":[{"name":"Department of Nephrology Monash Medical Centre Clayton Vic. 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