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Title: Bryostatin-1 Attenuates Ischemia-Elicited Neutrophil Transmigration and Ameliorates Graft Injury after Kidney Transplantation
Authors: Becker, F
Kebschull, L
Rieger, C
Mohr, A
Heitplatz, B
Van Marck, V
Hansen, U
Ansari, J
Reuter, S
Strücker, B
Pascher, A
Brockmann, JG
Castor, T
Alexander, JS
Gavins, FNE
Keywords: kidney transplant;ischemia reperfusion injury;Bryostatin-1;translational research
Issue Date: 10-Mar-2022
Publisher: MDPI AG
Citation: Becker, F., Kebschull, L., Rieger, C., Mohr, A., Heitplatz, B., Van Marck, V.,Hansen, U., Ansari, A., Reuter, S., Strücker, B., Pascher, A., Brockmann, J.G., Castor, T., Alexander, J.S. and Gavins, F.N.E. (2022) ‘Bryostatin-1 Attenuates Ischemia-Elicited Neutrophil Transmigration and Ameliorates Graft Injury after Kidney Transplantation’, Cells, 11 (6), 948, pp. 1 - 19. doi: 10.3390/cells11060948.
Abstract: Copyright: © 2022 by the authors. Ischemia reperfusion injury (IRI) is a form of sterile inflammation whose severity determines short- and long-term graft fates in kidney transplantation. Neutrophils are now recognized as a key cell type mediating early graft injury, which activates further innate immune responses and intensifies acquired immunity and alloimmunity. Since the macrolide Bryostatin-1 has been shown to block neutrophil transmigration, we aimed to determine whether these findings could be translated to the field of kidney transplantation. To study the effects of Bryostatin-1 on ischemia-elicited neutrophil transmigration, an in vitro model of hypoxia and normoxia was equipped with human endothelial cells and neutrophils. To translate these findings, a porcine renal autotransplantation model with eight hours of reperfusion was used to study neutrophil infiltration in vivo. Graft-specific treatment using Bryostatin-1 (100 nM) was applied during static cold storage. Bryostatin-1 dose-dependently blocked neutrophil activation and transmigration over ischemically challenged endothelial cell monolayers. When applied to porcine renal autografts, Bryostatin-1 reduced neutrophil graft infiltration, attenuated histological and ultrastructural damage, and improved renal function. Our novel findings demonstrate that Bryostatin-1 is a promising pharmacological candidate for graft-specific treatment in kidney transplantation, as it provides protection by blocking neutrophil infiltration and attenuating functional graft injury.
Description: Data Availability Statement: Not applicable.
Appears in Collections:Dept of Life Sciences Research Papers

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