title: The fibrinopeptide bβ15-42 reduces inflammation in mice subjected to polymicrobial sepsis.
abstract: Sepsis is still a leading cause of death on intensive care units. Despite intensive research, only few new therapies have been developed and used in the clinical setting. The fibrin fragment Bβ15-42 was already shown to preserve endothelial barrier function by binding to VE-cadherin and thus stabilize the interendothelial junctions. This was accompanied by reduced inflammation. Now we show that treatment with Bβ15-42 reduces inflammation in a murine polymicrobial sepsis model. Administration of Bβ15-42 reduced proinflammatory cytokine levels in the lung, liver, and blood and decreased neutrophil infiltration into the lung. Analysis alanine aminotransferase and aspartate aminotransferase further indicated reduced liver damage following polymicrobial sepsis. In vitro experiments using endothelial cells and macrophages further revealed that Bβ15-42 had no direct effect on Toll-like receptor-mediated inflammation. Therefore, we assume that attenuated inflammation is rather due to sustained vascular integrity and thus suppresses vascular leakage and subsequently leukocyte infiltration during sepsis.
authors: Clinic of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Germany.
authors: Carla
authors: C
authors: Jennewein
authors: Martina
authors: M
authors: Mehring
authors: Nguyen
authors: N
authors: Tran
authors: Patrick
authors: P
authors: Paulus
authors: Pia Alexandra
authors: PA
authors: Ockelmann
authors: Katharina
authors: K
authors: Habeck
authors: Kathrina
authors: K
authors: Latsch
authors: Bertram
authors: B
authors: Scheller
authors: Kai
authors: K
authors: Zacharowski
authors: Haitham
authors: H
authors: Mutlak
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects; D005338:Fibrin Fibrinogen Degradation Products / Q000494:pharmacology*; D007150:Immunohistochemistry; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D018805:Sepsis / Q000517:prevention & control*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; C033786:fibrinogen Bbeta (15-42)