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The aim of this study was to define the role of lymphocyte function antigen\u20101 (LFA\u20101) in regulating neutrophil\u2010endothelium interactions and tissue damage in severe AP.<\/jats:p><\/jats:sec><jats:sec><jats:title>EXPERIMENTAL APPROACH<\/jats:title><jats:p>Pancreatitis was induced by retrograde infusion of sodium taurocholate into the pancreatic duct in mice. LFA\u20101 gene\u2010targeted mice and an antibody directed against LFA\u20101 were used to define the role of LFA\u20101.<\/jats:p><\/jats:sec><jats:sec><jats:title>KEY RESULTS<\/jats:title><jats:p>Taurocholate challenge caused a clear\u2010cut increase in serum amylase, neutrophil infiltration, CXCL2 (macrophage inflammatory protein\u20102) formation, trypsinogen activation and tissue damage in the pancreas. Inhibition of LFA\u20101 function markedly reduced taurocholate\u2010induced amylase levels, accumulation of neutrophils, production of CXC chemokines and tissue damage in the pancreas. Notably, intravital microscopy revealed that inhibition of LFA\u20101 abolished taurocholate\u2010induced leucocyte adhesion in postcapillary venules of the pancreas. In addition, pulmonary infiltration of neutrophils was attenuated by inhibition of LFA\u20101 in mice challenged with taurocholate. However, interference with LFA\u20101 had no effect on taurocholate\u2010induced activation of trypsinogen in the pancreas.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS AND IMPLICATIONS<\/jats:title><jats:p>Our novel data suggest that LFA\u20101 plays a key role in regulating neutrophil recruitment, CXCL2 formation and tissue injury in the pancreas. Moreover, these results suggest that LFA\u20101\u2010mediated inflammation is a downstream component of trypsinogen activation in the pathophysiology of AP. Thus, we conclude that targeting LFA\u20101 may be a useful approach to protect against pathological inflammation in the pancreas.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1476-5381.2011.01225.x","type":"journal-article","created":{"date-parts":[[2011,1,19]],"date-time":"2011-01-19T07:14:17Z","timestamp":1295421257000},"page":"413-423","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Lymphocyte function antigen\u20101 regulates neutrophil recruitment and tissue damage in acute pancreatitis"],"prefix":"10.1111","volume":"163","author":[{"given":"Darbaz","family":"Awla","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aree","family":"Abdulla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Roller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D","family":"Menger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Regn\u00e9r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Thorlacius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,4,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.49.3.253"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e318162c567"},{"key":"e_1_2_8_4_1","first-page":"167","article-title":"Chemokines in disease models and pathogenesis","volume":"9","author":"Bacon KB","year":"1998","journal-title":"Cytokine Growth Factor Rev"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.regpep.2006.08.006"},{"key":"e_1_2_8_6_1","doi-asserted-by":"crossref","first-page":"2511","DOI":"10.4049\/jimmunol.162.5.2511","article-title":"Islet\u2010specific Th1, but not Th2, cells secrete multiple chemokines and promote rapid induction of autoimmune diabetes","volume":"162","author":"Bradley LM","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90279-8"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msg183"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.163.9.5029"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2008.05.010"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.1.336"},{"key":"e_1_2_8_12_1","first-page":"69","article-title":"Trypsin activation peptide (TAP) in acute pancreatitis: from pathophysiology to clinical usefulness","volume":"2","author":"Frossard JL","year":"2001","journal-title":"JOP"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70192-7"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.32409"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.3.911.003k36_911_920"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006676-199603000-00013"},{"key":"e_1_2_8_17_1","doi-asserted-by":"crossref","first-page":"6533","DOI":"10.4049\/jimmunol.154.12.6533","article-title":"In vivo blood monocyte migration to acute inflammatory reactions, IL\u20101 alpha, TNF\u2010alpha, IFN\u2010gamma, and C5a utilizes LFA\u20101, Mac\u20101, and VLA\u20104. 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