Possible Involvement of Toll-Like Receptor 4 in Endothelial Cell Activation of Larger Vessels in Response to Lipopolysaccharide

Pathobiology ◽  
2002 ◽  
Vol 70 (1) ◽  
pp. 18-25 ◽  
Author(s):  
Naoki Hijiya ◽  
Kensuke Miyake ◽  
Sachiko Akashi ◽  
Keiko Matsuura ◽  
Yasunori Higuchi ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Activation ◽  
Toll Like Receptor ◽  
Endothelial Cell Activation ◽  
Toll Like Receptor 4

Toll like Receptor 4 Is Involved in In VIvo Antiphospholipid-Mediated Thrombosis and Endothelial Cell Activation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 133-133
Author(s):  
Silvia S. Pierangeli ◽  
Mariano E. Vega-Ostertag ◽  
Elena Raschi ◽  
Xiaowei Liu ◽  
Maria O. Borghi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Antiphospholipid Syndrome ◽  
Cell Activation ◽  
Spontaneous Mutation ◽  
Toll Like Receptor ◽  
Endothelial Cell Activation ◽  
Toll Like Receptor 4 ◽  
Control Serum

Abstract Background: Antiphospholipid antibodies (aPL) are associated with thrombosis and pregnancy loss in patients with Antiphospholipid Syndrome (APS). aPL and bacterial lipopolysaccharide (LPS) bind to and activate endothelial cells (EC) through NFκB and p38 MAPK pathways. Recent studies suggest that aPL might interact with toll-like receptor-4 (TLR-4), the receptor for LPS. Aim: to investigate the role of TLR-4 in antiphospholipid syndrome (APS). Methods: we examined: i) the aPL effects on thrombosis and EC activation in LPS non-responsive (LPS−/−) mice that display a spontaneous mutation of TLR-4 vs LPS-responsive (LPS+/+) mice displaying wild type TLR-4, ii) the prevalence of TLR-4 Asp299gly and Thr399Ile polymorphisms - both associated with decreased response to LPS - in 110 APS patients (with arterial and/or venous thrombosis) vs 220 controls (of same ethnic background). IgGs were purified from a patient with APS (IgG-APS) and from control serum (IgG-NHS). LPS −/− and LPS +/+ mice, in groups of nine, were treated with IgG-APS or with IgG-NHS twice intraperitoneally. Size of induced thrombi and # of leukocyte (WBC) adhering to endothelial cells in the microcirculation of endothelium of the cremaster muscle of mice (as a means to measure endothelial cell activation) were determined in vivo, seventy-two hours after the first injection. TLR-4 Asp299gly & Thr399Ile polymorphisms were evaluated by Allele-Specific PCR. Results: LPS +/+ mice treated with IgG-APS produced significantly larger thrombi when compared to mice treated with IgG-NHS (2166 ± 1419 μm2 vs 1176 ± 841 μm2) and significantly larger number of WBC adherence to ECs (4.5 ± 1.9 vs 2.2 ±1.1). Thrombus size and number of adhering WBC to ECs were significantly lower in LPS −/− mice treated with IgG-APS compared to LPS +/+ mice treated with IgG-APS [thrombus size: 779 ± 628 μm2 vs 2166 ± 1419 μm2 (p<0.05) and number of adherent WBC to EC: 1.0 ± 0.5 vs 4.5 1.9 (p<0.05)], respectively. The titer of anticardiolipin antibodies in the sera of mice injected with aPL was 48.2 ± 17.1 GPL (for LPS −/− mice) and 50.8 ± 11.2 GPL (for LPS +/+ mice), respectively (NS). A significant reduction in TLR-4 Asp 299gly & Thr399Ile polymorphisms was observed in APS patients (5%) compared to controls (11.4%) (p<0.05). Conclusions: These findings strongly suggest that TLR-4 is involved in aPL interaction with endothelial cells and mediates their pathogenic effects.

scholarly journals Platelet disturbances correlate with endothelial cell activation in uncomplicated Plasmodium vivax malaria

2020 ◽  
Vol 14 (7) ◽  
pp. e0007656
Author(s):  
João Conrado Khouri Dos-Santos ◽  
João Luiz Silva-Filho ◽  
Carla C. Judice ◽  
Ana Carolina Andrade Vitor Kayano ◽  
Júlio Aliberti ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Cell Activation ◽  
Endothelial Cell Activation ◽  
Plasmodium Vivax Malaria

scholarly journals Signs of sympathetic and endothelial cell activation in the skin of patients with restless legs syndrome

2021 ◽  
Author(s):  
Melanie Bergmann ◽  
Anna Heidbreder ◽  
Ambra Stefani ◽  
Cecilia Raccagni ◽  
Elisabeth Brandauer ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Restless Legs Syndrome ◽  
Cell Activation ◽  
Endothelial Cell Activation ◽  
Restless Legs

OR17 Heme oxygenase-1 modulates HLA class I antibody-dependent endothelial cell activation

2015 ◽  
Vol 76 ◽  
pp. 15
Author(s):  
Eva Zilian ◽  
Hendry Saragih ◽  
Oliver Hiller ◽  
Abid Aljabri ◽  
Constanca Figueiredo ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Heme Oxygenase ◽  
Cell Activation ◽  
Hla Class I ◽  
Class I ◽  
Heme Oxygenase 1 ◽  
Endothelial Cell Activation

scholarly journals Dengue Virus Induces the Expression and Release of Endocan from Endothelial Cells by an NS1–TLR4-Dependent Mechanism

2021 ◽  
Vol 9 (6) ◽  
pp. 1305
Author(s):  
Carlos Alonso Domínguez-Alemán ◽  
Luis Alberto Sánchez-Vargas ◽  
Karina Guadalupe Hernández-Flores ◽  
Andrea Isabel Torres-Zugaide ◽  
Arturo Reyes-Sandoval ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Mrna Expression ◽  
Cell Lines ◽  
Cell Activation ◽  
Dengue Infection ◽  
Elevated Serum ◽  
Fold Increase ◽  
Endothelial Cell Activation ◽  
Stimulation Of

A common hallmark of dengue infections is the dysfunction of the vascular endothelium induced by different biological mechanisms. In this paper, we studied the role of recombinant NS1 proteins representing the four dengue serotypes, and their role in promoting the expression and release of endocan, which is a highly specific biomarker of endothelial cell activation. We evaluated mRNA expression and the levels of endocan protein in vitro following the stimulation of HUVEC and HMEC-1 cell lines with recombinant NS1 proteins. NS1 proteins increase endocan mRNA expression 48 h post-activation in both endothelial cell lines. Endocan mRNA expression levels were higher in HUVEC and HMEC-1 cells stimulated with NS1 proteins than in non-stimulated cells (p < 0.05). A two-fold to three-fold increase in endocan protein release was observed after the stimulation of HUVECs or HMEC-1 cells with NS1 proteins compared with that in non-stimulated cells (p < 0.05). The blockade of Toll-like receptor 4 (TLR-4) signaling on HMEC-1 cells with an antagonistic antibody prevented NS1-dependent endocan production. Dengue-infected patients showed elevated serum endocan levels (≥30 ng/mL) during early dengue infection. High endocan serum levels were associated with laboratory abnormalities, such as lymphopenia and thrombocytopenia, and are associated with the presence of NS1 in the serum.

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