L-Fucose prevention of renal ischaemia/reperfusion injury in Mice.

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.

SUBMITTER: Howard MC 

PROVIDER: S-EPMC6972607 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature