The vimentin rod domain blocks P-selectin-P-selectin glycoprotein ligand 1 interactions to attenuate leukocyte adhesion to inflamed endothelium

PLoS One. 2020 Oct 13;15(10):e0240164. doi: 10.1371/journal.pone.0240164. eCollection 2020.


Acute inflammation begins with leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) binding to P-selectin on inflamed endothelium and platelets. In pathologic conditions, this process may contribute to secondary organ damage, like sepsis-induced liver injury. Therefore, developing novel therapies to attenuate inflammation may be beneficial. We previously reported that recombinant human vimentin (rhVim) binds P-selectin to block leukocyte adhesion to endothelium and platelets. In this study, we used SPOT-peptide arrays to identify the rod domain as the active region within rhVim that interacts with P-selectin. Indeed, recombinant human rod domain of vimentin (rhRod) binds to P-selectin with high affinity, with in silico modeling suggesting that rhRod binds P-selectin at or near the PSGL-1 binding site. Using bio-layer interferometry, rhRod decreases PSGL-1 binding to immobilized P-selectin, corroborating the in silico data. Under parallel-plate flow, rhRod blocks leukocyte adhesion to fibrin(ogen)-captured platelets, P-selectin/Fc-coated channels, and IL-1β/IL-4-co-stimulated human umbilical vein endothelial cells. Finally, using intravital microscopy in endotoxemic C57Bl/6 mice, rhRod co-localizes with P-selectin in the hepatic sinusoids and decreases neutrophil adhesion to hepatic sinusoids. These data suggest a potential role for rhRod in attenuating inflammation through directly blocking P-selectin-PSGL-1 interactions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Adhesion / drug effects*
  • Cell Adhesion / immunology
  • Disease Models, Animal
  • Endothelium / drug effects
  • Endothelium / immunology
  • Endotoxemia / drug therapy*
  • Endotoxemia / immunology
  • Endotoxemia / pathology
  • Female
  • Healthy Volunteers
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Interferometry
  • Leukocytes / drug effects
  • Leukocytes / immunology*
  • Male
  • Membrane Glycoproteins / metabolism*
  • Molecular Docking Simulation
  • P-Selectin / metabolism*
  • Protein Binding / drug effects
  • Protein Binding / immunology
  • Protein Domains / genetics
  • Recombinant Proteins / genetics
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • Vimentin / genetics
  • Vimentin / pharmacology*
  • Vimentin / therapeutic use


  • Membrane Glycoproteins
  • P-Selectin
  • P-selectin ligand protein
  • Recombinant Proteins
  • VIM protein, human
  • Vimentin