Vimentin is an endogenous ligand for the pattern recognition receptor Dectin-1.

Cardiovascular Research

PubMedID: 23674515

Thiagarajan PS, Yakubenko VP, Elsori DH, Yadav SP, Willard B, Tan CD, Rodriguez ER, Febbraio M, Cathcart MK. Vimentin is an endogenous ligand for the pattern recognition receptor Dectin-1. Cardiovasc Res. 2013;99(3):494-504.
AIMS
Atherosclerosis is a chronic inflammatory disorder of cholesterol deposition in monocyte-derived macrophages (MDM) within the arterial wall leading to impingement on the lumen of the vessel. In atherosclerotic lesions, MDM are the primary source of NADPH oxidase-derived superoxide anion (O2(-)) inducing low-density lipoprotein (LDL) oxidation leading to their unregulated uptake of oxidized LDL and foam cell formation. We recently discovered that zymosan potently activates monocyte NADPH oxidase via the non-toll pattern recognition receptor (PRR), Dectin-1. Other PRRs bind endogenous human ligands, yet no such ligands have been identi?ed for Dectin-1. Our hypothesis was that in?ammation generates endogenous ligands for Dectin-1 that activate O2(-) production and thereby contributes to atherogenesis.

METHODS AND RESULTS
Human: anti-zymosan antibodies were used to identify similar, cross-reactive epitopes in human atherosclerotic tissue extracts. Immunoblot analysis revealed consistent antibody reactive protein bands on one- and two-dimensional gel electrophoreses. Vimentin was identified by mass spectrometry in the immunoreactive bands across different tissue samples. Direct binding of vimentin to Dectin-1 was observed using BIACORE. Further data revealed that vimentin induces O2(-) production by human monocytes. Analysis of human atherosclerotic lesions revealed that vimentin was detected extracellularly in the necrotic core and in areas of active inflammation. Vimentin also co-localized with Dectin-1 in macrophage-rich regions where O2(-) is produced.

CONCLUSION
We conclude that vimentin is an endogenous, activating ligand for Dectin-1. Its presence in areas of artery wall inflammation and O2(-) production suggests that vimentin activates Dectin-1 and contributes to the oxidation of lipids and cholesterol accumulation in atherosclerosis.