Adenosine inhibits cytokine release and expression of adhesion molecules by activated human endothelial cells

1996 ◽  
Vol 270 (2) ◽  
pp. C522-C529 ◽  
Author(s):  
M. G. Bouma ◽  
F. A. van den Wildenberg ◽  
W. A. Buurman
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Vascular Endothelium ◽  
Cell Activation ◽  
Umbilical Vein ◽  
Intercellular Adhesion Molecule ◽  
Cytokine Release ◽  
Adenosine Deaminase Activity ◽  
Anti Inflammatory

Ischemia induces excessive ATP catabolism with subsequent local release of its metabolite adenosine, an autacoid with anti-inflammatory properties. Because activation of the vascular endothelium is critical to the inflammatory host response during ischemia and reperfusion, the effects of adenosine on two major determinants of endothelial cell activation (i.e., the release of proinflammatory cytokines and the expression of adhesion molecules) were studied. Adenosine dose dependently inhibited the release of interleukin (IL)-6 and IL-8 by stimulated human umbilical vein endothelial cells (HUVEC). Expression of E-selectin and vascular cell adhesion molecule 1 (VCAM-1), but not intercellular adhesion molecule 1 (ICAM-1), by activated HUVEC was also reduced by adenosine. Inhibition of endogenous adenosine deaminase activity by erythro-9-(2-hydroxy-3-nonyl)adenine or 2'-deoxycoformycin strongly enhanced the inhibitory effects of exogenous adenosine on cytokine release and expression of E-selectin and VCAM-1. However, a clear role for specific adenosine receptors in the described inhibitory events could not be established. Together, these data imply that the vascular endothelium constitutes an important target for the anti-inflammatory actions of adenosine.

scholarly journals Intercellular adhesion molecule-1 mediates the expression of monocyte- derived MIP-1 alpha during monocyte-endothelial cell interactions

Blood ◽  
1994 ◽  
Vol 83 (5) ◽  
pp. 1174-1178 ◽  
Author(s):  
NW Lukacs ◽  
RM Strieter ◽  
VM Elner ◽  
HL Evanoff ◽  
M Burdick ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Adhesion Molecule ◽  
Cell Activation ◽  
Specific Binding ◽  
Umbilical Vein ◽  
Cellular Adhesion ◽  
Cell Interactions ◽  
Intercellular Adhesion Molecule ◽  
Alpha Production

Abstract The extravasation of leukocytes from the lumen of the vessel to a site of inflammation initially requires a specific binding event followed by migration of the cells through the endothelial cell layer into the inflammatory foci. The interaction of leukocytes with the endothelium via specific receptors may provide intracellular signals that activate the cells. In the present study we have investigated the production of MIP-1 alpha, a mononuclear cell chemotactic protein, during monocyte:endothelial cell interactions. Neither unstimulated nor interferon (IFN)-stimulated human umbilical vein endothelial cells (HUVECs) produced substantial MIP-1 alpha protein. However, the addition of enriched monocyte populations with unstimulated HUVECs resulted in the production of MIP-1 alpha. Monocytes cultured with IFN- gamma-activated HUVECs showed an additional increase in MIP-1 alpha production. Immunohistochemical analysis demonstrated that the monocyte was the cellular source of MIP-1 alpha production in this coculture system. The mechanism of MIP-1 alpha expression was further assessed by determining the role of adhesion molecules in the regulation of MIP-1 alpha production during monocyte:HUVEC interactions. To attenuate the increased production of MIP-1 alpha by the monocyte:HUVEC interaction, anti-adhesion molecule monoclonal antibodies (MoAbs) were added to the cultures. Addition of anti-ICAM-1 neutralizing MoAbs significantly inhibited the production of MIP-1 alpha, whereas neutralizing anti-VCAM- 1 MoAbs failed to block MIP-1 alpha production. Furthermore, MIP-1 alpha production was induced in monocytes cultured on ICAM-1-coated plates. These results indicate an intimate relationship between leukocyte-endothelial cells, adhesion molecule, and the expression of the monocyte-derived chemokine MIP-1 alpha during cellular adhesion. This mechanism may serve an important role in cell activation and recruitment of leukocytes during the initiation of an inflammatory response.

scholarly journals Expression of functional CD40 by vascular endothelial cells.

1995 ◽  
Vol 182 (1) ◽  
pp. 33-40 ◽  
Author(s):  
D Hollenbaugh ◽  
N Mischel-Petty ◽  
C P Edwards ◽  
J C Simon ◽  
R W Denfeld ◽  
...  
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Inflammatory Disease ◽  
Vascular Endothelium ◽  
Cell Activation ◽  
Inflammatory Responses ◽  
Vascular Endothelial Cells ◽  
Intercellular Adhesion Molecule ◽  
Vascular Endothelial

The interaction between activated vascular endothelium and T cells has been shown to play an important role in the recruitment and activation of T cells at sites of inflammation. Here we report the expression of CD40 by vascular endothelial cells and its regulation by inflammatory agents. Using the soluble recombinant CD40 ligand, sgp39, we show that the interaction of CD40 with its ligand can lead to endothelial cell activation, which in turn leads to leukocyte adhesion. This adhesion is partly mediated by the expression of E-selectin. In addition to E-selectin expression, sgp39 induces the expression of intercellular adhesion molecule 1 and augments the tumor necrosis factor alpha-induced expression of vascular cell adhesion molecule 1. The effects of sgp39 on endothelial cells can be blocked with anti-gp39 monoclonal antibody (mAb), anti-CD40 mAb, or soluble CD40. Staining of tissues from healthy human skin using anti-CD40 mAb showed very weak expression of CD40 by the endothelium, while skin involved in inflammatory disease showed marked upregulation of CD40 expression. These studies suggest that interactions between cell surface proteins expressed by activated T cells with their receptors on vascular endothelium can stimulate the vasculature at sites of inflammation and may be involved in normal inflammatory responses and in inflammatory disease.

Increases in oxygen tension stimulate expression of ICAM-1 and VCAM-1 on human endothelial cells

1999 ◽  
Vol 276 (6) ◽  
pp. H2044-H2052 ◽  
Author(s):  
Carsten Willam ◽  
Ralf Schindler ◽  
Ulrich Frei ◽  
Kai-Uwe Eckardt
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Umbilical Vein ◽  
Ischemia Reperfusion ◽  
White Blood Cells ◽  
Free Radical Scavengers ◽  
Intercellular Adhesion Molecule ◽  
Induced Expression ◽  
Tnf Α

Leukocyte infiltration plays a major role in ischemia-associated organ dysfunction and damage. A crucial step for extravasation of white blood cells is binding of leukocyte β-integrins to endothelial adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1). To test for direct effects of oxygen on this process we studied ICAM-1 and VCAM-1 expression in human dermal microvascular and umbilical vein endothelial cells (EC) exposed to different oxygen tensions in the absence or presence of tumor necrosis factor-α (TNF-α). Hypoxia (95% N2-5% CO2) resulted in a downregulation of basal but not TNF-α-induced expression of ICAM-1 and VCAM-1. Subsequent rises in oxygen (21, 40, or 95% O2) led to marked increase of ICAM-1 and VCAM-1 cell surface and mRNA expression in both EC types, which after 16 h amounted to about one-third to one-half of maximal TNF-α-induced expression. This increase was greatest after 0.5-h hypoxia and was blunted with prolonged hypoxic preincubation. Exposure of cells preincubated under “normoxic” (21% O2) conditions to hyperoxia (40 or 95% O2) also enhanced expression of both adhesion molecules, but the increase was lower than in cells preexposed to hypoxia. The nitric oxide synthesis inhibitor NG-nitro-l-arginine methyl ester (l-NAME) enhanced ICAM-1 and VCAM-1 expression under basal and hypoxic conditions, but in the presence of l-NAME, levels in reoxygenated cells were not higher than basal levels. Moreover, the oxygen-induced rise could be mimicked by addition of H2O2to normoxic cells, and the oxygen-induced expression of VCAM-1 but not of ICAM-1 was inhibited by addition of the free radical scavengers superoxide dismutase, N-acetyl-l-cysteine, and pyrrolidinedithiocarbamate. These data indicate that an increase in oxygen availability stimulates ICAM-1 and VCAM-1 expression on micro- and macrovascular EC, which may contribute to adhesion and transmigration of different leukocyte populations in ischemia-reperfusion injuries.

scholarly journals The Nutraceutical Dehydrozingerone and Its Dimer Counteract Inflammation- and Oxidative Stress-Induced Dysfunction ofIn VitroCultured Human Endothelial Cells: A Novel Perspective for the Prevention and Therapy of Atherosclerosis

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Elisabetta Profumo ◽  
Brigitta Buttari ◽  
Daniela D’Arcangelo ◽  
Lavinia Tinaburri ◽  
Maria Antonietta Dettori ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Antioxidant Activities ◽  
Umbilical Vein ◽  
Intercellular Adhesion Molecule ◽  
Ros Production ◽  
Atherosclerosis Progression ◽  
Anti Inflammatory ◽  
And Oxidative Stress

Atherosclerosis is characterized by endothelial dysfunction, mainly induced by inflammation and oxidative stress. Increased reactive oxygen species (ROS) production together with increased adhesion molecules and thrombogenic tissue factor (TF) expression on endothelial cells has a key role in proatherogenic mechanisms. Therefore downmodulation of these molecules could be useful for reducing the severity of inflammation and atherosclerosis progression. Dehydrozingerone (DHZ) is a nutraceutical compound with anti-inflammatory and antioxidant activities. In this study we evaluated the ability of DHZ and its symmetric dimer to modulate hydrogen peroxide- (H2O2-) induced ROS production in human umbilical vein endothelial cells (HUVEC). We also evaluated intercellular adhesion molecule- (ICAM-) 1, vascular cell adhesion molecule- (VCAM-) 1, and TF expression in HUVEC activated by tumor necrosis factor- (TNF-)α. HUVEC pretreatment with DHZ and DHZ dimer reduced H2O2-induced ROS production and inhibited adhesion molecule expression and secretion. Of note, only DHZ dimer was able to reduce TF expression. DHZ effects were in part mediated by the inhibition of the nuclear factor- (NF-)κB activation. Overall, our findings demonstrate that the DHZ dimer exerts a potent anti-inflammatory, antioxidant, and antithrombotic activity on endothelial cells and suggest potential usefulness of this compound to contrast the pathogenic mechanisms involved in atherosclerosis progression.

scholarly journals Intercellular adhesion molecule-1 mediates the expression of monocyte- derived MIP-1 alpha during monocyte-endothelial cell interactions

Blood ◽  
1994 ◽  
Vol 83 (5) ◽  
pp. 1174-1178
Author(s):  
NW Lukacs ◽  
RM Strieter ◽  
VM Elner ◽  
HL Evanoff ◽  
M Burdick ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Adhesion Molecule ◽  
Cell Activation ◽  
Specific Binding ◽  
Umbilical Vein ◽  
Cellular Adhesion ◽  
Cell Interactions ◽  
Intercellular Adhesion Molecule ◽  
Alpha Production

The extravasation of leukocytes from the lumen of the vessel to a site of inflammation initially requires a specific binding event followed by migration of the cells through the endothelial cell layer into the inflammatory foci. The interaction of leukocytes with the endothelium via specific receptors may provide intracellular signals that activate the cells. In the present study we have investigated the production of MIP-1 alpha, a mononuclear cell chemotactic protein, during monocyte:endothelial cell interactions. Neither unstimulated nor interferon (IFN)-stimulated human umbilical vein endothelial cells (HUVECs) produced substantial MIP-1 alpha protein. However, the addition of enriched monocyte populations with unstimulated HUVECs resulted in the production of MIP-1 alpha. Monocytes cultured with IFN- gamma-activated HUVECs showed an additional increase in MIP-1 alpha production. Immunohistochemical analysis demonstrated that the monocyte was the cellular source of MIP-1 alpha production in this coculture system. The mechanism of MIP-1 alpha expression was further assessed by determining the role of adhesion molecules in the regulation of MIP-1 alpha production during monocyte:HUVEC interactions. To attenuate the increased production of MIP-1 alpha by the monocyte:HUVEC interaction, anti-adhesion molecule monoclonal antibodies (MoAbs) were added to the cultures. Addition of anti-ICAM-1 neutralizing MoAbs significantly inhibited the production of MIP-1 alpha, whereas neutralizing anti-VCAM- 1 MoAbs failed to block MIP-1 alpha production. Furthermore, MIP-1 alpha production was induced in monocytes cultured on ICAM-1-coated plates. These results indicate an intimate relationship between leukocyte-endothelial cells, adhesion molecule, and the expression of the monocyte-derived chemokine MIP-1 alpha during cellular adhesion. This mechanism may serve an important role in cell activation and recruitment of leukocytes during the initiation of an inflammatory response.

scholarly journals Fimbria-Dependent Activation of Cell Adhesion Molecule Expression in Porphyromonas gingivalis-Infected Endothelial Cells

2002 ◽  
Vol 70 (1) ◽  
pp. 257-267 ◽  
Author(s):  
Mary Khlgatian ◽  
Hamdy Nassar ◽  
Hsin-Hua Chou ◽  
Frank C. Gibson ◽  
Caroline Attardo Genco
Keyword(s):  
Endothelial Cells ◽  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Porphyromonas Gingivalis ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Inflammatory Diseases ◽  
Umbilical Vein ◽  
Intercellular Adhesion Molecule ◽  
Adhesion Molecule Expression

ABSTRACT Porphyromonas gingivalis is an oral pathogen that has recently been associated with chronic inflammatory diseases such as atherosclerosis. The strength of the epidemiological associations of P. gingivalis with atherosclerosis can be increased by the demonstration that P. gingivalis can initiate and sustain growth in human vascular cells. We previously established that P. gingivalis can invade aortic, heart, and human umbilical vein endothelial cells (HUVEC), that fimbriae are required for invasion of endothelial cells, and that fimbrillin peptides can induce the expression of the chemokines interleukin 8 and monocyte chemotactic protein. In this study, we examined the expression of surface-associated cell adhesion molecules on endothelial cells in response to P. gingivalis infection by fluorescence-activated cell sorting FACS analysis and confocal microscopy. Coculture of HUVEC with P. gingivalis strain 381 or A7436 resulted in the induction in the expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and P- and E-selectins, which was maximal at 48 h postinfection. In contrast, we did not observe induction of ICAM-1, VCAM-1, or P- or E-selectin expression in HUVEC cultured with the noninvasive P. gingivalis fimA mutant DPG3 or when P. gingivalis was incubated with fimbrillin peptide-specific anti-sera prior to the addition to HUVEC. Furthermore, the addition of a peptide corresponding to the N-terminal domain of fimbrillin to HUVEC resulted in an increase in ICAM-1, VCAM-1, and P- and E-selectins, which was maximal at 48 h and similar to that observed for live P. gingivalis. Treatment of P. gingivalis-infected HUVEC with cytochalsin D, which prevented P. gingivalis invasion, also resulted in the inhibition of ICAM-1, VCAM-1, or P- and E-selectin expression. Taken together, these results indicate that active P. gingivalis invasion of HUVEC mediated via the major fimbriae stimulates surface-associated cell adhesion molecule expression. Stimulation of adhesion molecules involved in the recruitment of leukocytes to sites of inflammation by P. gingivalis may play a role in the pathogenesis of systemic inflammatory diseases associated with this microorganism, including atherosclerosis.

scholarly journals Direct Activation of Human Endothelial Cells by Plasmodium falciparum-Infected Erythrocytes

2005 ◽  
Vol 73 (6) ◽  
pp. 3271-3277 ◽  
Author(s):  
Nicola K. Viebig ◽  
Ulrich Wulbrand ◽  
Reinhold Förster ◽  
Katherine T. Andrews ◽  
Michael Lanzer ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Plasmodium Falciparum ◽  
Endothelial Cell ◽  
Adhesion Molecule ◽  
Cell Activation ◽  
Physical Contact ◽  
Intercellular Adhesion Molecule ◽  
Immune Reactivity ◽  
Human Endothelial Cells ◽  
Tnf Α

ABSTRACT Cytoadherence of Plasmodium falciparum-infected erythrocytes (PRBC) to endothelial cells causes severe clinical disease, presumably as a of result perfusion failure and tissue hypoxia. Cytoadherence to endothelial cells is increased by endothelial cell activation, which is believed to occur in a paracrine fashion by mediators such as tumor necrosis factor alpha (TNF-α) released from macrophages that initially recognize PRBC. Here we provide evidence that PRBC directly stimulate human endothelial cells in the absence of macrophages, leading to increased expression of adhesion-promoting molecules, such as intercellular adhesion molecule 1. Endothelial cell stimulation by PRBC required direct physical contact for a short time (30 to 60 min) and was correlated with parasitemia. Gene expression profiling of endothelial cells stimulated by PRBC revealed increased expression levels of chemokine and adhesion molecule genes. PRBC-stimulated endothelial cells especially showed increased expression of molecules involved in parasite adhesion but failed to express molecules promoting leukocyte adhesion, such as E-selectin and vascular cell adhesion molecule 1, even after challenge with TNF-α. Collectively, our data suggest that stimulation of endothelial cells by PRBC may have two effects: prevention of parasite clearance through increased cytoadherence and attenuation of leukocyte binding to endothelial cells, thereby preventing deleterious immune reactivity.

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