The secreted Ly6/uPAR-related protein-1 suppresses neutrophil binding, chemotaxis, and transmigration through human umbilical vein endothelial cells
| Autor: | Sudha Swamynathan, Vishal Jhanji, Nicholas Alexander, Anil Tiwari, Shivalingappa K. Swamynathan, Chelsea L. Loughner, John Gnalian |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Neutrophils lcsh:Medicine HL-60 Cells Umbilical vein Article 03 medical and health sciences 0302 clinical medicine Cell Movement Cell Adhesion Human Umbilical Vein Endothelial Cells Antigens Ly Humans Protein kinase A Cell adhesion lcsh:Science Protein kinase B Multidisciplinary Chemistry lcsh:R Chemotaxis Urokinase-Type Plasminogen Activator Cell biology Endothelial stem cell Urokinase receptor Chemotaxis Leukocyte 030104 developmental biology Tumor necrosis factor alpha lcsh:Q E-Selectin 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-11 (2019) |
| ISSN: | 2045-2322 |
| Popis: | The secreted Ly-6/uPAR Related Protein-1 (SLURP1) is an immunomodulatory protein that promotes corneal immune- and angiogenic-privilege. Here, we have examined the influence of SLURP1 on neutrophil-vascular endothelial cell interactions using human umbilical vein endothelial cells (HUVEC) and differentiated neutrophil-like HL-60 (dHL-60) cells, or primary human neutrophils. SLURP1 blocked the tumor necrosis factor-alpha (TNF-α)-activated dHL-60 cells (i) binding to TNF-α-activated HUVEC with a concurrent reduction in endothelial cell adhesion molecule E-selectin, (ii) transmigration through TNF-α-activated confluent HUVEC monolayer by stabilizing VE-cadherin and β-catenin on endothelial cell cytoplasmic membranes, (iii) chemotaxis towards chemoattractant formyl Met-Leu-Phe (fMLP) coupled with their decreased polarization, and (iv) TNF-α-stimulated matrix metalloproteinase-9 (MMP9) expression and activity. SLURP1 also suppressed the primary human neutrophil chemotaxis, and interaction with HUVEC. Furthermore, SLURP1 suppressed fMLP-induced phosphorylation of protein kinase-B (AKT) in dHL-60 cells. Collectively, these results provide evidence that SLURP1 suppresses neutrophil (i) docking on HUVEC cells by decreasing endothelial cell adhesion molecule E-Selectin production, (ii) transmigration through HUVEC monolayer by stabilizing endothelial cell membrane localization of VE-cadherin and β-catenin complex and promoting their barrier function, and (iii) chemotaxis by modulating their polarization and TNF-α-stimulated MMP9 production. |
| Databáze: | OpenAIRE |
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