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l-Fucose prevention of renal ischaemia/reperfusion injury in Mice
journal contributionposted on 2020-05-22, 12:25 authored by Mark C Howard, Christopher L Nauser, Conrad A Farrar, Russell Wallis, Steven H Sacks
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.
This work was supported by Medical Research Council (MRC) grant MR/M012263/1:Collectin‐11 as a trigger of the innate immune response in renal transplantation.
CitationHoward, MC, Nauser, CL, Farrar, CA, Wallis, R, Sacks, SH. l ‐Fucose prevention of renal ischaemia/reperfusion injury in Mice. The FASEB Journal. 2020; 34: 822– 834. https://doi.org/10.1096/fj.201901582R
- VoR (Version of Record)
Published inFASEB JOURNAL
Pagination822 - 834 (13)
PublisherFEDERATION AMER SOC EXP BIOL
Science & TechnologyLife Sciences & BiomedicineBiochemistry & Molecular BiologyBiologyCell BiologyLife Sciences & Biomedicine - Other Topicscollectin-11complementischemiareperfusionl-fucoselectin pathwaytransplantationISCHEMIA-REPERFUSION INJURYDELAYED GRAFT FUNCTIONCOLLECTIN 11 CL-11LECTIN PATHWAYCOMPLEMENTCOMPLEXESCL-K1MASPSCL-L1