scholarly journals Shiga Toxin Selectively Upregulates Expression of Syndecan-4 and Adhesion Molecule ICAM-1 in Human Glomerular Microvascular Endothelium

Toxins ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 435
Author(s):  
Elena B. Volokhina ◽  
Wouter J. C. Feitz ◽  
Lonneke M. Elders ◽  
Thea J. A. M. van der Velden ◽  
Nicole C. A. J. van de Kar ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Shiga Toxin ◽  
Alternative Pathway ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Microvascular Endothelium ◽  
Protein Levels

Hemolytic uremic syndrome (HUS) is a severe renal disease that is often preceded by infection with Shiga toxin (Stx)-producing Escherichia coli (STEC). The exact mechanism of Stx-mediated inflammation on human glomerular microvascular endothelial cells (HGMVECs) during HUS is still not well understood. In this study, we investigated the effect of Stx1 on the gene expression of proteins involved in leucocyte-mediated and complement-mediated inflammation. Our results showed that Stx1 enhances the mRNA and protein expression of heparan sulfate proteoglycan (HSPG) syndecan-4 in HGMVECs pre-stimulated with tumor necrosis factor α (TNFα). CD44 was upregulated on mRNA but not on protein level; no effect on the mRNA expression of other tested HSPGs glypican-1 and betaglycan was observed. Furthermore, Stx1 upregulated the mRNA, cell surface expression, and supernatant levels of the intercellular adhesion molecule-1 (ICAM-1) in HGMVECs. Interestingly, no effect on the protein levels of alternative pathway (AP) components was observed, although C3 mRNA was upregulated. All observed effects were much stronger in HGMVECs than in human umbilical endothelial cells (HUVECs), a common model cell type used in endothelial studies. Our results provide new insights into the role of Stx1 in the pathogenesis of HUS. Possibilities to target the overexpression of syndecan-4 and ICAM-1 for STEC-HUS therapy should be investigated in future studies.

Action of cAMP on expression and release of adhesion molecules in human endothelial cells

1996 ◽  
Vol 270 (3) ◽  
pp. H807-H816 ◽  
Author(s):  
R. Morandini ◽  
G. Ghanem ◽  
A. Portier-Lemarie ◽  
B. Robaye ◽  
A. Renaud ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Umbilical Vein ◽  
Mrna Level ◽  
Phosphodiesterase Inhibitor ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Soluble E Selectin

The expression of E-selectin induced by tumor necrosis factor (TNF) on the surface of human umbilical vein endothelial cells (HUVEC) was partially inhibited by an increase in the level of adenosine 3',5'-cyclic monophosphate (cAMP), produced by forskolin or cholera toxin combined with the type IV phosphodiesterase inhibitor rolipram and the protein kinase A agonist phosphorothioate analogue of cAMP SpcAMPS. The same agents had no significant effect on the constitutive and TNF-stimulated expression of intercellular adhesion molecule 1 (ICAM-1), whereas the effect on vascular cell adhesion molecule 1 (VCAM-1) expression was variable depending on cell culture conditions. The stimulatory effects of phorbol 12-myristate 13-acetate and bacterial lipopolysaccharide (LPS) on E-selectin expression were also downregulated by the forskolin-rolipram combination and by SpcAMPS. Inhibition of the surface expression of E-selectin was associated with a decrease of the total amount of the protein in the cell lysate and a reduced mRNA level, with no significant effect on mRNA stability. In anesthetized rats, the terbutaline-rolipram combination reduced the rolling of leukocytes induced by LPS in the mesenteric microcirculation. In addition to their partial inhibitory effect on the TNF-induced surface expression of E-selectin on HUVEC, the forskolin-rolipram combination and SpcAMPS strongly inhibited the release of soluble E-selectin from these cells; the release of soluble ICAM-1 and VCAM-1 was unaffected by these agents. Isoproterenol reduced the release of soluble E-selectin, whereas it had no significant effect on the cell surface expression of the protein. This study underscores the potential anti-inflammatory effect of a rise in the endothelial cAMP level.

scholarly journals Listeria monocytogenes Virulence Factors That Stimulate Endothelial Cells

1998 ◽  
Vol 66 (1) ◽  
pp. 232-238 ◽  
Author(s):  
Douglas A. Drevets
Keyword(s):  
Endothelial Cells ◽  
Listeria Monocytogenes ◽  
Adhesion Molecule ◽  
Surface Expression ◽  
Cytochalasin D ◽  
Intercellular Adhesion Molecule ◽  
Neutrophil Adhesion ◽  
Listeriolysin O ◽  
Wild Type ◽  
Intercellular Adhesion Molecule 1

ABSTRACT Listeria monocytogenes infection of endothelial cells upregulates surface expression of adhesion molecules and stimulates neutrophil adhesion to infected cell monolayers. The experiments presented here tested the roles of specific bacterial virulence factors as triggers for this inflammatory phenotype and function. Human umbilical vein endothelial cell (HUVEC) monolayers were infected with wild-type L. monocytogenes or L. monocytogenesmutants; then surface expression of E-selectin and neutrophil adhesion were measured. The results showed that Δhly andprfA mutants were the most crippled, requiring 100-fold more mutant bacteria than wild-type bacteria for analogous stimulation. By comparison, L. monocytogenes mutants with deletions ofactA, inlA, inlB,inlAB, plcA, and plcB resembled their parent strains, and a ΔplcA ΔplcB mutant displayed decreased intracellular growth rate but only a minor decrease in stimulation of E-selectin or neutrophil adhesion. Other experiments showed that cytochalasin D-treated HUVEC monolayers bound bacteria, but internalization and increased surface E-selectin and intercellular adhesion molecule-1 expression were profoundly inhibited. However, cytochalasin D had no effect on the HUVEC response to stimulation with lipopolysaccharide or tumor necrosis factor alpha. These data suggest that listeriolysin O production by infecting L. monocytogenes contributes to increased expression of surface E-selectin and intercellular adhesion molecule-1, but neither it nor intracellular replication are directly responsible for this event. Nonetheless it is possible that listeriolysin O potentiates the effect(s) of an other molecule(s) that directly triggers this response. Additionally, cellular invasion by L. monocytogenes appears to be critical for initiating the HUVEC response, potentially by providing a signal which results in upregulation of the necessary bacterial genes.

XO increases neutrophil adherence to endothelial cells by a dual ICAM-1 and P-selectin-mediated mechanism

1997 ◽  
Vol 82 (3) ◽  
pp. 866-873 ◽  
Author(s):  
Lance S. Terada ◽  
Brooks M. Hybertson ◽  
Kevin G. Connelly ◽  
David Weill ◽  
Dale Piermattei ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Platelet Activating Factor ◽  
Surface Expression ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Neutrophil Adherence ◽  
Adhesive Interactions ◽  
Static Conditions

Terada, Lance S., Brooks M. Hybertson, Kevin G. Connelly, David Weill, Dale Piermattei, and John E. Repine. XO increases neutrophil adherence to endothelial cells by a dual ICAM-1 and P-selectin-mediated mechanism. J. Appl. Physiol. 82(3): 866–873, 1997.—Circulating xanthine oxidase (XO) can modify adhesive interactions between neutrophils and the vascular endothelium, although the mechanisms underlying this effect are not clear. We found that treatment with XO of bovine pulmonary artery endothelial cells (EC), but not neutrophils or plasma, increased adherence, suggesting that XO had its primary effect on EC. The mechanism by which XO increased neutrophil adherence to EC involved binding of XO to EC and production of H2O2. XO also increased platelet-activating factor production by EC by a H2O2-dependent mechanism. Similarly, the platelet-activating factor-receptor antagonist WEB-2086 completely blocked XO-mediated neutrophil EC adherence. In addition, neutrophil adherence was dependent on the β2-integrin Mac-1 (CD11b/CD18) but not on leukocyte functional antigen-1 (CD11a/CD18). Treatment of EC with XO for 30 min did not alter intercellular adhesion molecule-1 surface expression but increased expression of P-selectin and release of von Willibrand factor. Antibodies against P-selectin (CD62) did not affect XO-mediated neutrophil adherence under static conditions but decreased both rolling and firm adhesive interactions under conditions of shear. We conclude that extracellular XO associates with the endothelium and promotes neutrophil-endothelial cell interactions through dual intercellular adhesion molecule-1 and P-selectin ligation, by a mechanism that involves platelet-activating factor and H2O2as intermediates.

Differential monocyte adhesion and adhesion molecule expression in venous and arterial endothelial cells

1999 ◽  
Vol 276 (1) ◽  
pp. L9-L19 ◽  
Author(s):  
Theodore J. Kalogeris ◽  
Christopher G. Kevil ◽  
F. Stephen Laroux ◽  
Laura L. Coe ◽  
Travis J. Phifer ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Interleukin 1 ◽  
Surface Expression ◽  
Nuclear Factor Κb ◽  
Intercellular Adhesion Molecule ◽  
Nuclear Factor ◽  
Adhesion Molecule Expression ◽  
Intercellular Adhesion Molecule 1

We compared U-937 cell adhesion and adhesion molecule expression in human umbilical venous (HUVECs) and arterial (HUAECs) endothelial cells exposed to tumor necrosis factor (TNF), interleukin-1, and lipopolysaccharide (LPS). TNF and LPS stimulated vascular cell adhesion molecule (VCAM)-1 surface expression and adhesion of U-937 monocyte-like cells to HUVECs but not to HUAECs. Antibody studies demonstrated that in HUVECs at least 75% of the adhesion response is VCAM-1 mediated. Interleukin-1 stimulated U-937 cell adhesion to and VCAM-1 surface expression in both HUVECs and HUAECs. Pyrrolidinedithiocarbamate and the proteasome inhibitor MG-132 blocked TNF- and LPS-stimulated U-937 cell adhesion to HUVECs. These agents also significantly decreased TNF- and LPS-stimulated increases in HUVEC surface VCAM-1. TNF increased VCAM-1 protein and mRNA in HUVECs that was blocked by pyrrolidinedithiocarbamate. However, neither TNF or LPS stimulated VCAM-1 expression in HUAECs. TNF stimulated expression of both intercellular adhesion molecule-1 and E-selectin in HUVECs, but in HUAECs, only intercellular adhesion molecule-1 was increased. Electrophoretic mobility shift assays demonstrated no difference in the pattern of TNF-stimulated nuclear factor-κB activation between HUVECs and HUAECs. These studies demonstrate a novel and striking insensitivity of arterial endothelium to the effects of TNF and LPS and indicate a dissociation between the ability of HUAECs to upregulate nuclear factor-κB and VCAM-1.

Synergism of multiple adhesion molecules in mediating cytoadherence of Plasmodium falciparum–infected erythrocytes to microvascular endothelial cells under flow

Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2292-2298 ◽  
Author(s):  
Bryan G. Yipp ◽  
Samantha Anand ◽  
Tineke Schollaardt ◽  
Kamala D. Patel ◽  
Sornchai Looareesuwan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Plasmodium Falciparum ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Oncostatin M ◽  
Intercellular Adhesion Molecule ◽  
Microvascular Endothelial Cells ◽  
Intercellular Adhesion Molecule 1 ◽  
Microvascular Endothelium ◽  
Microvascular Endothelial

Plasmodium falciparum–infected erythrocytes (IRBCs) have been shown to interact with a number of endothelial adhesion molecules expressed on transfectants, on cell lines, and as immobilized purified receptor proteins under flow conditions. However, the experiments were designed in such a way that maximal numbers of adhesion molecules were provided as substratum. Whether the interactive events actually occur on microvascular endothelium, where the distribution and expression of adhesion molecules may be less, remains undetermined. In this study, the cytoadherance of IRBCs on human dermal microvascular endothelial cells (HDMECs) as a model of human microvasculature was examined. IRBCs were observed to tether, roll, and adhere on resting HDMECs, which constitutively expressed CD36 and intercellular adhesion molecule-1 (ICAM-1) at an optimal shear stress of 1 dyne/cm2. Stimulation of HDMECs with tumor necrosis factor–α for 5 and 24 hours, which resulted in up-regulation of ICAM-1 and induction of vascular cell adhesion molecule-1 expression, significantly increased the percentage of rolling cells that adhered without affecting the rolling flux. In contrast, P-selectin expression on HDMECs induced by oncostatin M led to an increase in both rolling flux and adhesion. Inhibition studies with receptor-specific monoclonal antibodies revealed that adhesion of IRBCs on HDMECs was largely CD36 dependent, whereas rolling could be mediated by any of the adhesion molecules studied. Collectively, these findings indicate that IRBCs interact synergistically with multiple adhesion molecules on vascular endothelium. The rolling of IRBCs may be the rate-limiting step in cytoadherance, since it can be modulated by cytokines to enhance CD36-mediated IRBC adhesion.

Synergism of multiple adhesion molecules in mediating cytoadherence of Plasmodium falciparum–infected erythrocytes to microvascular endothelial cells under flow

Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2292-2298 ◽  
Author(s):  
Bryan G. Yipp ◽  
Samantha Anand ◽  
Tineke Schollaardt ◽  
Kamala D. Patel ◽  
Sornchai Looareesuwan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Plasmodium Falciparum ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Oncostatin M ◽  
Intercellular Adhesion Molecule ◽  
Microvascular Endothelial Cells ◽  
Intercellular Adhesion Molecule 1 ◽  
Microvascular Endothelium ◽  
Microvascular Endothelial

Abstract Plasmodium falciparum–infected erythrocytes (IRBCs) have been shown to interact with a number of endothelial adhesion molecules expressed on transfectants, on cell lines, and as immobilized purified receptor proteins under flow conditions. However, the experiments were designed in such a way that maximal numbers of adhesion molecules were provided as substratum. Whether the interactive events actually occur on microvascular endothelium, where the distribution and expression of adhesion molecules may be less, remains undetermined. In this study, the cytoadherance of IRBCs on human dermal microvascular endothelial cells (HDMECs) as a model of human microvasculature was examined. IRBCs were observed to tether, roll, and adhere on resting HDMECs, which constitutively expressed CD36 and intercellular adhesion molecule-1 (ICAM-1) at an optimal shear stress of 1 dyne/cm2. Stimulation of HDMECs with tumor necrosis factor–α for 5 and 24 hours, which resulted in up-regulation of ICAM-1 and induction of vascular cell adhesion molecule-1 expression, significantly increased the percentage of rolling cells that adhered without affecting the rolling flux. In contrast, P-selectin expression on HDMECs induced by oncostatin M led to an increase in both rolling flux and adhesion. Inhibition studies with receptor-specific monoclonal antibodies revealed that adhesion of IRBCs on HDMECs was largely CD36 dependent, whereas rolling could be mediated by any of the adhesion molecules studied. Collectively, these findings indicate that IRBCs interact synergistically with multiple adhesion molecules on vascular endothelium. The rolling of IRBCs may be the rate-limiting step in cytoadherance, since it can be modulated by cytokines to enhance CD36-mediated IRBC adhesion.

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