l-Fucose prevention of renal ischaemia/reperfusion injury in Mice.
FASEB J
; 34(1): 822-834, 2020 01.
Article
em En
| MEDLINE
| ID: mdl-31914693
ABSTRACT
In a recent study, we identified a fucosylated damage-associated ligand exposed by ischemia on renal tubule epithelial cells, which after recognition by collectin-11 (CL-11 or collectin kidney 1 (CL-K1)), initiates complement activation and acute kidney injury. We exploited the ability to increase the local tissue concentration of free l-fucose following systemic administration, in order to block ligand binding by local CL-11 and prevent complement activation. We achieved a thirty-five-fold increase in the intrarenal concentration of l-fucose following an IP bolus given before the ischemia induction procedure - a concentration found to significantly block in vitro binding of CL-11 on hypoxia-stressed renal tubule cells. At this l-fucose dose, complement activation and acute post-ischemic kidney injury are prevented, with additional protection achieved by a second bolus after the induction procedure. CL-11-/- mice gained no additional protection from l-fucose administration, indicating that the mechanism of l-fucose therapy was largely CL-11-dependent. The hypothesis is that a high dose of l-fucose delivered to the kidney obstructs the carbohydrate recognition site on CL-11 thereby reducing complement-mediated damage following ischemic insult. Further work will examine the utility in preventing post-ischemic injury during renal transplantation, where acute kidney injury is known to correlate with poor graft survival.
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Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão
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Ativação do Complemento
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Fucose
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Isquemia
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article