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


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

SUBMITTER: Thiagarajan PS 

PROVIDER: S-EPMC3718321 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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

Thiagarajan Praveena S PS   Yakubenko Valentin P VP   Elsori Deena H DH   Yadav Satya P SP   Willard Belinda B   Tan Carmela D CD   Rodriguez E René ER   Febbraio Maria M   Cathcart Martha K MK  

Cardiovascular research 20130513 3


<h4>Aims</h4>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 NAD  ...[more]

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