{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:05:54Z","timestamp":1792667154387,"version":"4.5.0"},"reference-count":44,"publisher":"American Diabetes Association","issue":"4","license":[{"start":{"date-parts":[[2017,3,21]],"date-time":"2017-03-21T00:00:00Z","timestamp":1490054400000},"content-version":"vor","delay-in-days":71,"URL":"http:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["1R01-DK-105183"],"award-info":[{"award-number":["1R01-DK-105183"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,4,1]]},"abstract":"<jats:p>Islet cell transplantation has limited effectiveness because of an instant blood-mediated inflammatory reaction (IBMIR) that occurs immediately after cell infusion and leads to dramatic \u03b2-cell death. In intraportal islet transplantation models using mouse and human islets, we demonstrated that \u03b1-1 antitrypsin (AAT; Prolastin-C), a serine protease inhibitor used for the treatment of AAT deficiency, inhibits IBMIR and cytokine-induced inflammation in islets. In mice, more diabetic recipients reached normoglycemia after intraportal islet transplantation when they were treated with AAT compared with mice treated with saline. AAT suppressed blood-mediated coagulation pathways by diminishing tissue factor production, reducing plasma thrombin-antithrombin complex levels and fibrinogen deposition on islet grafts, which correlated with less graft damage and apoptosis. AAT-treated mice showed reduced serum tumor necrosis factor-\u03b1 levels, decreased lymphocytic infiltration, and decreased nuclear factor (NF)-\u03baB activation compared with controls. The potent anti-inflammatory effect of AAT is possibly mediated by suppression of c-Jun N-terminal kinase (JNK) phosphorylation. Blocking JNK activation failed to further reduce cytokine-induced apoptosis in \u03b2-cells. Taken together, AAT significantly improves islet graft survival after intraportal islet transplantation by mitigation of coagulation in IBMIR and suppression of cytokine-induced JNK and NF-\u03baB activation. AAT-based therapy has the potential to improve graft survival in human islet transplantation and other cellular therapies on the horizon.<\/jats:p>","DOI":"10.2337\/db16-1036","type":"journal-article","created":{"date-parts":[[2017,1,10]],"date-time":"2017-01-10T02:15:16Z","timestamp":1484014516000},"page":"970-980","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":82,"title":["\u03b1-1 Antitrypsin Enhances Islet Engraftment by Suppression of Instant Blood-Mediated Inflammatory Reaction"],"prefix":"10.2337","volume":"66","author":[{"given":"Jingjing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Surgery, Medical University of South Carolina, Charleston, SC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical University of South Carolina, Charleston, SC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyu","family":"Gou","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical University of South Carolina, Charleston, SC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Adams","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical University of South Carolina, Charleston, SC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanxing","family":"Cui","sequence":"additional","affiliation":[{"name":"MedStar Georgetown University Hospital, Washington, DC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Morgan","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical University of South Carolina, Charleston, SC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlie","family":"Strange","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medical University of South Carolina, Charleston, SC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical University of South Carolina, Charleston, SC"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2017,1,9]]},"reference":[{"key":"2022031210394438800_B1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s00534-008-0021-2","article-title":"Current status of islet cell transplantation","volume":"16","author":"Ichii","year":"2009","journal-title":"J Hepatobiliary Pancreat Surg"},{"key":"2022031210394438800_B2","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1097\/TP.0b013e3182845fbb","article-title":"Prior surgery determines islet yield and insulin requirement in patients with chronic pancreatitis","volume":"95","author":"Wang","year":"2013","journal-title":"Transplantation"},{"key":"2022031210394438800_B3","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1172\/JCI116297","article-title":"Beta cell mass and growth after syngeneic islet cell transplantation in normal and streptozocin diabetic C57BL\/6 mice","volume":"91","author":"Monta\u00f1a","year":"1993","journal-title":"J Clin Invest"},{"key":"2022031210394438800_B4","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.2337\/diab.45.9.1161","article-title":"Vulnerability of islets in the immediate posttransplantation period. 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