Journal Article

Collectin-11 detects stress-induced L-fucose pattern to trigger renal epithelial injury

Tran, David, Peng, Qi, Wu, Weiju, Sacks, Steven H., Li, Ke, Zhou, Wuding, Schwaeble, Wilhelm, Farrar, Conrad A.

2016

Overview

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.

• Publisher: American Society for Clinical Investigation
• Subject: Acute Kidney Injury - chemically induced / Acute Kidney Injury - genetics / Acute Kidney Injury - metabolism / Acute Kidney Injury - pathology / Analysis / Animals / Biological markers / Biomedical research / Collectins - genetics / Collectins - metabolism / Complement Pathway, Mannose-Binding Lectin - drug effects / Complement Pathway, Mannose-Binding Lectin - genetics / Complement System Proteins - genetics / Complement System Proteins - metabolism / Diagnosis / Experiments / Flow cytometry / Fucose - toxicity / Gangrene / Ischemia / Kidney diseases / Kidney Tubules, Proximal - injuries / Kidney Tubules, Proximal - metabolism / Kidney Tubules, Proximal - pathology / Kidneys / Lectins / Ligands / Localization / Mannose-Binding Protein-Associated Serine Proteases - genetics / Mannose-Binding Protein-Associated Serine Proteases - metabolism / Mice / Mice, Knockout / Proteases / Rodents / Software