A1: Early barrier dysfunction after experimental and clinical polytrauma

PI: M. Huber-Lang

After polytrauma, the cellular and molecular danger response may initiate blood-organ barrier dysfunction, often leading to multiple organ failure and death. However, little is known about the underlying mechanisms of trauma-induced barrier breakdown and thus effective therapeutic approaches. Therefore, a first study goal will define markers indicative of early barrier dysfunction in polytraumatised patients. In experimental polytrauma, organ-specific development of barrier dysfunction will be morphologically assessed and correlated to organ function and immune response. In serum of polytrauma patients, potential barrier markers will be related to clinical data on immune and organ performance. As a second goal, underlying mechanisms of barrier breakdown as a result of the inflammatory response will be elucidated in various in vitro barrier models. After exposure of endothelial and epithelial cells to trauma-relevant danger molecules (e.g. complement activation products C3a, C5a, HMGB-1, trauma sera) tight junction proteins in corresponding cells and supernatant fluids will be determined. In a third goal, the effectiveness of promising immune-modulators (e.g. C5a inhibitors) in reducing tight junction breakdown will be tested in vivo to propose a clinically relevant therapeutic strategy to improve barrier function and outcome post trauma.



Prof. Dr. med. Markus Huber-Lang
Universitätsklinikum Ulm
Zentrum für ChirurgieKlinik für Unfallchirurgie, Hand-, Plastische und Wiederherstellungschirurgie
Zentrum für Biomedizinische Forschung (ZBF)
Helmholtzstr. 8/2
89081 Ulm
Tel.: +49 731 500 54716
Fax: +49 731 500 54718

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