Inhibition of Syk activity by R788 in platelets prevents remote lung tissue damage after mesenteric ischemia-reperfusion injury

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dc.authoridLapchak, Peter/0000-0001-8597-088X
dc.authoridIoannou, Antonis/0000-0003-0064-5004
dc.authorwosidLapchak, Peter H./B-3559-2009
dc.authorwosidLapchak, Peter H./JCE-0582-2023
dc.authorwosidtsokos, george C/O-3360-2013
dc.contributor.authorLapchak, Peter H.
dc.contributor.authorKannan, Lakshmi
dc.contributor.authorRani, Poonam
dc.contributor.authorPamuk, Omer Nuri
dc.contributor.authorIoannou, Antonis
dc.contributor.authorLucca, Jurandir J. Dalle
dc.contributor.authorPine, Polly
dc.date.accessioned2024-06-12T11:07:55Z
dc.date.available2024-06-12T11:07:55Z
dc.date.issued2012
dc.departmentTrakya Üniversitesien_US
dc.description.abstractLapchak PH, Kannan L, Rani P, Pamuk ON, Ioannou A, Lucca JJ, Pine P, Tsokos GC. Inhibition of Syk activity by R788 in platelets prevents remote lung tissue damage after mesenteric ischemia-reperfusion injury. Am J Physiol Gastrointest Liver Physiol 302: G1416-G1422, 2012. First published April 5, 2012; doi: 10.1152/ajpgi.00026.2012.-Tissue injury following ischemia-reperfusion (I/R) occurs as a consequence of actions of soluble factors and immune cells. Growing evidence supports a role for platelets in the manifestation of tissue damage following I/R. Spleen tyrosine kinase has been well documented to be important in lymphocyte activation and more recently in platelet activation. We performed experiments to evaluate whether inhibition of platelet activation through inhibition of spleen tyrosine kinase prevents tissue damage after mesenteric I/R injury. Platelets isolated from C57BL/6J mice fed with R788 for 10 days were transfused into C57BL/6J mice depleted of platelets 2 days before mesenteric I/R injury. Platelet-depleted mice transfused with platelets from R788-treated mice before mesenteric I/R displayed a significant reduction in the degree of remote lung damage, but with little change in the degree of local intestinal damage compared with control I/R mice. Transfusion of R788-treated platelets also decreased platelet sequestration, C3 deposition, and immunoglobulin deposition in lung, but not in the intestine, compared with control groups. These findings demonstrate that platelet activation is a requisite for sequestration in the pulmonary vasculature to mediate remote tissue injury after mesenteric I/R. The use of small-molecule inhibitors may be valuable to prevent tissue damage in remote organs following I/R injury.en_US
dc.description.sponsorshipMedical Research and Material Command of the Department of the Army [W81XWH-09-1-0530, W81XWH-09-1-0536]en_US
dc.description.sponsorshipThe research presented herein was supported by Grant nos. W81XWH-09-1-0530 and W81XWH-09-1-0536 from Medical Research and Material Command of the Department of the Army.en_US
dc.identifier.doi10.1152/ajpgi.00026.2012
dc.identifier.endpageG1422en_US
dc.identifier.issn0193-1857
dc.identifier.issn1522-1547
dc.identifier.issue12en_US
dc.identifier.pmid22492694en_US
dc.identifier.scopus2-s2.0-84862512151en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpageG1416en_US
dc.identifier.urihttps://doi.org/10.1152/ajpgi.00026.2012
dc.identifier.urihttps://hdl.handle.net/20.500.14551/22237
dc.identifier.volume302en_US
dc.identifier.wosWOS:000305398600007en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherAmer Physiological Socen_US
dc.relation.ispartofAmerican Journal Of Physiology-Gastrointestinal And Liver Physiologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectLungsen_US
dc.subjectTissue Injuryen_US
dc.subjectIntestineen_US
dc.subjectPlatelet Depletionen_US
dc.subjectPlatelet Transfusionen_US
dc.subjectSpleen Tyrosine Kinaseen_US
dc.subjectEndothelial-Cellsen_US
dc.subjectLeukocyte Interactionsen_US
dc.subjectFunctional Expressionen_US
dc.subjectCd40 Liganden_US
dc.subjectComplementen_US
dc.subjectActivationen_US
dc.subjectDiseaseen_US
dc.subjectStrokeen_US
dc.subjectIschemia/Reperfusionen_US
dc.titleInhibition of Syk activity by R788 in platelets prevents remote lung tissue damage after mesenteric ischemia-reperfusion injuryen_US
dc.typeArticleen_US

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