title: Collectin-11 detects stress-induced L-fucose pattern to trigger renal epithelial injury.
abstract: Physiochemical stress induces tissue injury as a result of the detection of abnormal molecular patterns by sensory molecules of the innate immune system. Here, we have described how the recently discovered C-type lectin collectin-11 (CL-11, also known as CL-K1 and encoded by COLEC11) recognizes an abnormal pattern of L-fucose on postischemic renal tubule cells and activates a destructive inflammatory response. We found that intrarenal expression of CL-11 rapidly increases in the postischemic period and colocalizes with complement deposited along the basolateral surface of the proximal renal tubule in association with L-fucose, the potential binding ligand for CL-11. Mice with either generalized or kidney-specific deficiency of CL-11 were strongly protected against loss of renal function and tubule injury due to reduced complement deposition. Ex vivo renal tubule cells showed a marked capacity for CL-11 binding that was induced by cell stress under hypoxic or hypothermic conditions and prevented by specific removal of L-fucose. Further analysis revealed that cell-bound CL-11 required the lectin complement pathway-associated protease MASP-2 to trigger complement deposition. Given these results, we conclude that lectin complement pathway activation triggered by ligand-CL-11 interaction in postischemic tissue is a potent source of acute kidney injury and is amenable to sugar-specific blockade.
authors.forename: Conrad A
authors.initials: CA
authors.lastname: Farrar
authors.forename: David
authors.initials: D
authors.lastname: Tran
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.forename: Weiju
authors.initials: W
authors.lastname: Wu
authors.forename: Qi
authors.initials: Q
authors.lastname: Peng
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Schwaeble
authors.forename: Wuding
authors.initials: W
authors.lastname: Zhou
authors.forename: Steven H
authors.initials: SH
authors.lastname: Sacks
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D037222:Collectins / Q000235:genetics / Q000378:metabolism*; D037582:Complement Pathway, Mannose-Binding Lectin / Q000187:drug effects* / Q000235:genetics; D003165:Complement System Proteins / Q000235:genetics / Q000378:metabolism*; D005643:Fucose / Q000633:toxicity*; D007687:Kidney Tubules, Proximal / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout
chemical_list: D037222:Collectins; D005643:Fucose; D003165:Complement System Proteins; C491340:MASP-2 protein, mouse; D050606:Mannose-Binding Protein-Associated Serine Proteases