BACKGROUND: Adherens junctions are critically important in control of endothelial cell permeability. Bβ15-42 is a peptide product of fibrin degradation that binds to vascular endothelial cadherin, the major component of endothelial adherens junctions. We tested the hypothesis that Bβ15-42 improves lung function in our rat lung transplant model. METHODS: Bβ15-42 was administered to donors before lung retrieval and to recipients by continuous intravenous infusion, or just to recipients, or neither. Recipients were monitored, anesthetized and ventilated, for 6 hours. Outcome measures were indices of lung function (edema [wet-to-dry weight ratio], oxygenation, dynamic compliance) and bronchoalveolar fluid measures of inflammation (protein, cell count, differential, and cytokines). RESULTS: Bβ15-42 therapy was associated with improved graft lung function, including less edema, and improved oxygenation and airway pressure, particularly if Bβ15-42 was administered to both the donor and recipient. However, Bβ15-42 had little or no effect on bronchoalveolar fluid measures of inflammation. Analysis of bronchoalveolar fluid protein concentration showed Bβ15-42 may enhance alveolar fluid clearance. CONCLUSIONS: Bβ15-42 may be a useful therapy to reduce edema and improve graft function after lung transplant, alone or as an adjunct to other therapies.
BACKGROUND: Adherens junctions are critically important in control of endothelial cell permeability. Bβ15-42 is a peptide product of fibrin degradation that binds to vascular endothelial cadherin, the major component of endothelial adherens junctions. We tested the hypothesis that Bβ15-42 improves lung function in our rat lung transplant model. METHODS: Bβ15-42 was administered to donors before lung retrieval and to recipients by continuous intravenous infusion, or just to recipients, or neither. Recipients were monitored, anesthetized and ventilated, for 6 hours. Outcome measures were indices of lung function (edema [wet-to-dry weight ratio], oxygenation, dynamic compliance) and bronchoalveolar fluid measures of inflammation (protein, cell count, differential, and cytokines). RESULTS: Bβ15-42 therapy was associated with improved graft lung function, including less edema, and improved oxygenation and airway pressure, particularly if Bβ15-42 was administered to both the donor and recipient. However, Bβ15-42 had little or no effect on bronchoalveolar fluid measures of inflammation. Analysis of bronchoalveolar fluid protein concentration showed Bβ15-42 may enhance alveolar fluid clearance. CONCLUSIONS: Bβ15-42 may be a useful therapy to reduce edema and improve graft function after lung transplant, alone or as an adjunct to other therapies.
Authors: Klaudia Schossleitner; Andreas Habertheuer; Richard Finsterwalder; Heinz P Friedl; Sabine Rauscher; Marion Gröger; Alfred Kocher; Christine Wagner; Stephan N Wagner; Gottfried Fischer; Marcus J Schultz; Dominik Wiedemann; Peter Petzelbauer Journal: PLoS One Date: 2015-11-04 Impact factor: 3.240