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          Institute: MPI für molekulare Biomedizin     Collection: Yearbook 2013     Display Documents



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ID: 648358.0, MPI für molekulare Biomedizin / Yearbook 2013
Cardiopulmonary bypass during cardiac surgery modulates systemic inflammation by affecting different steps of the leukocyte recruitment cascade
Authors:Rossaint, J.; Berger, C.; Van Aken, H.; Scheld, H. H.; Zahn, P. K.; Rukosujew, A.; Zarbock, A.
Date of Publication (YYYY-MM-DD):2012
Title of Journal:PLoS ONE
Volume:7
Issue / Number:9
Start Page:e45738
Review Status:Internal review
Audience:Not Specified
Abstract / Description:BACKGROUND: It is known that the use of a cardiopulmonary bypass (CPB) during cardiac surgery leads to leukocyte activation and may, among other causes, induce organ dysfunction due to increased leukocyte recruitment into different organs. Leukocyte extravasation occurs in a cascade-like fashion, including capturing, rolling, adhesion, and transmigration. However, the molecular mechanisms of increased leukocyte recruitment caused by CPB are not known. This clinical study was undertaken in order to investigate which steps of the leukocyte recruitment cascade are affected by the systemic inflammation during CPB. METHODS: We investigated the effects of CPB on the different steps of the leukocyte recruitment cascade in whole blood from healthy volunteers (n = 9) and patients undergoing cardiac surgery with the use of cardiopulmonary bypass (n = 7) or in off-pump coronary artery bypass-technique (OPCAB, n = 9) by using flow chamber experiments, transmigration assays, and biochemical analysis. RESULTS: CPB abrogated selectin-induced slow leukocyte rolling on E-selectin/ICAM-1 and P-selectin/ICAM-1. In contrast, chemokine-induced arrest and transmigration was significantly increased by CPB. Mechanistically, the abolishment of slow leukocyte rolling was due to disturbances in intracellular signaling with reduced phosphorylation of phospholipase C (PLC) gamma2, Akt, and p38 MAP kinase. Furthermore, CPB induced an elevated transmigration which was caused by upregulation of Mac-1 on neutrophils. CONCLUSION: These data suggest that CPB abrogates selectin-mediated slow leukocyte rolling by disturbing intracellular signaling, but that the clinically observed increased leukocyte recruitment caused by CPB is due to increased chemokine-induced arrest and transmigration. A better understanding of the underlying molecular mechanisms causing systemic inflammation after CPB may aid in the development of new therapeutic approaches.
External Publication Status:published
Document Type:Article
Communicated by:keuker
Affiliations:MPI für molekulare Biomedizin
External Affiliations:%G eng
Identifiers:ISSN:1932-6203 (Electronic) 1932-6203 (Linking) %R 10.1... [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/pubmed/23029213 [ID No:2]
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