Recombinant Human Vimentin Binds to P-Selectin and Blocks Neutrophil Capture and Rolling on Platelets and Endothelium

Lam, Fong; Da, Qi; Guillory, Bobby; Crúz, Miguel A.

doi:10.4049/jimmunol.1700784

Cited by 48 publications

(60 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, extracellular vimentin has been shown to have a role in inflamed tissue in atherosclerosis [ 183 ] and to interact with von Willebrand factor in platelets [ 184 ]. Specifically, vimentin reduces the adhesion of human leucocytes to platelets and the endothelium by binding to P-selectin on leukocytes and endothelial cells, which resulted in the suggestion to use recombinant vimentin to attenuate inflammation [ 185 ].…”

Section: Vimentin: Functionmentioning

confidence: 99%

Vimentin Diversity in Health and Disease

Danielsson

Peterson

Araújo

et al. 2018

Cells

211

204

View full text Add to dashboard Cite

Vimentin is a protein that has been linked to a large variety of pathophysiological conditions, including cataracts, Crohn’s disease, rheumatoid arthritis, HIV and cancer. Vimentin has also been shown to regulate a wide spectrum of basic cellular functions. In cells, vimentin assembles into a network of filaments that spans the cytoplasm. It can also be found in smaller, non-filamentous forms that can localise both within cells and within the extracellular microenvironment. The vimentin structure can be altered by subunit exchange, cleavage into different sizes, re-annealing, post-translational modifications and interacting proteins. Together with the observation that different domains of vimentin might have evolved under different selection pressures that defined distinct biological functions for different parts of the protein, the many diverse variants of vimentin might be the cause of its functional diversity. A number of review articles have focussed on the biology and medical aspects of intermediate filament proteins without particular commitment to vimentin, and other reviews have focussed on intermediate filaments in an in vitro context. In contrast, the present review focusses almost exclusively on vimentin, and covers both ex vivo and in vivo data from tissue culture and from living organisms, including a summary of the many phenotypes of vimentin knockout animals. Our aim is to provide a comprehensive overview of the current understanding of the many diverse aspects of vimentin, from biochemical, mechanical, cellular, systems biology and medical perspectives.

show abstract

Section: Vimentin: Functionmentioning

confidence: 99%

Vimentin Diversity in Health and Disease

Danielsson

Peterson

Araújo

et al. 2018

Cells

211

204

View full text Add to dashboard Cite

show abstract

“…Protein expression and purification were performed as before [14]. The sequence NM_00380.3 (NCBI) was used to synthesize both full-length human vimentin (base pairs 418-1,814) and the rhRod (base pairs 717-1,652; aa residues 96-407).…”

Section: Generation Of Full-length (Rhvim) and The Rod Domain (Rhrod)mentioning

confidence: 99%

“…Citrated whole blood was collected from healthy human subjects to study whole blood (3.2% sodium citrate) or isolated neutrophil (iPMN; citrate phosphate dextrose). To evaluate neutrophils, citrated blood was processed as before to isolate neutrophils [1,14]. Briefly, erythrocytes were sedimented using dextran in sodium chloride.…”

Section: Leukocyte and Isolated Neutrophil Collectionmentioning

confidence: 99%

“…HUVEC were prepared and seeded onto Bioflux microfluidic chambers as before [14]. Briefly, P3-P5 HUVEC were cultured in T75 flasks until >90% confluence before passage onto fibronectin (100 μg/mL)-coated channels.…”

Section: Huvec Preparationmentioning

confidence: 99%

“…Although the effect of native circulating vimentin is unclear, we published that exogenous recombinant human vimentin (rhVim) decreases human leukocyte adhesion to platelets and endothelial cells in vitro and reduces lung inflammation in endotoxemic mice. This reduction in leukocyte adhesion is through rhVim binding specifically to P-selectin [14]. However, the binding regions on both P-selectin and rhVim to produce those observations were unknown.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2020

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Mechanical and Non‐Mechanical Functions of Filamentous and Non‐Filamentous Vimentin

et al. 2020

View full text Add to dashboard Cite

Intermediate filaments (IFs) formed by vimentin are less understood than their cytoskeletal partners, microtubules and F-actin, but the unique physical properties of IFs, especially their resistance to large deformations, initially suggest a mechanical function. Indeed, vimentin IFs help regulate cell mechanics and contractility, and in crowded 3D environments they protect the nucleus during cell migration. Recently, a multitude of studies, often using genetic or proteomic screenings show that vimentin has many non-mechanical functions within and outside of cells. These include signaling roles in wound healing, lipogenesis, sterol processing, and various functions related to extracellular and cell surface vimentin. Extracellular vimentin is implicated in marking circulating tumor cells, promoting neural repair, and mediating the invasion of host cells by viruses, including SARS-CoV, or bacteria such as Listeria and Streptococcus. These findings underscore the fundamental role of vimentin in not only cell mechanics but also a range of physiological functions. Also see the video abstract here https://youtu.be/ YPfoddqvz-g.

show abstract

Recombinant Human Vimentin Binds to P-Selectin and Blocks Neutrophil Capture and Rolling on Platelets and Endothelium

Cited by 48 publications

References 46 publications

Vimentin Diversity in Health and Disease

Vimentin Diversity in Health and Disease

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

Mechanical and Non‐Mechanical Functions of Filamentous and Non‐Filamentous Vimentin

Contact Info

Product

Resources

About