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

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.

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Exogenous NO enhances hydrogen peroxide-mediated neutrophil adherence to cultured endothelial cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1998.274.5.l820 ◽

1998 ◽

Vol 274 (5) ◽

pp. L820-L826 ◽

Cited By ~ 4

Author(s):

Naotsuka Okayama ◽

Hiroshi Ichikawa ◽

Laura Coe ◽

Makoto Itoh ◽

J. Steven Alexander

Keyword(s):

Hydrogen Peroxide ◽

Endothelial Cells ◽

Adhesion Molecule ◽

Platelet Activating Factor ◽

Intercellular Adhesion ◽

Intercellular Adhesion Molecule ◽

Adhesion Assay ◽

Intercellular Adhesion Molecule 1 ◽

No Donor ◽

Cultured Endothelial Cells

One important aspect of oxidant injury is the enhancement of neutrophil-endothelial adhesion by oxidants such as hydrogen peroxide. Recent studies suggest that nitric oxide (NO) can limit oxidant-mediated tissue injury, since inhibitors of endogenous NO synthesis often promote neutrophil-endothelial adhesion. However, less is known about the direct role of exogenous NO in modulating proadhesive effects of oxidants. The objective of this study was to examine how an NO donor modifies hydrogen peroxide-mediated adhesion of neutrophils to cultured endothelial cells. Human umbilical vein endothelial cell monolayers were exposed for 30 min to 0–0.1 mM hydrogen peroxide with or without the NO donor spermine-NONOate (SNO; 0–0.5 mM), and the adhesion of51Cr-labeled polymorphonuclear neutrophils (PMNs) was measured in a static adhesion assay. PMN adherence was not altered by either peroxide (up to 0.1 mM) or SNO (up to 0.5 mM) alone but was significantly increased by over 300% by coadministration of both 0.1 mM peroxide and 0.5 mM SNO. This increase in adhesion with these two agents was correlated with an increase in the presentation of surface P-selectin but not intercellular adhesion molecule-1. Both PMN adhesion and P-selectin presentation were blocked by 0.1 mM desferrioxamine (an iron chelator) and 1 mM methionine (an oxy-radical scavenger). WEB-2086, a platelet-activating factor-receptor antagonist (10 μM), also prevented PMN adhesion but not P-selectin expression. An antibody directed against either P-selectin or intercellular adhesion molecule-1 also blocked adhesion. These data indicate that NO may actually exacerbate rather than protect against the inflammatory effects of peroxide in some models of inflammation through the synthesis of platelet-activating factor and the mobilization of P-selectin.

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Activated Platelets Induce Monocyte Chemotactic Protein-1 Secretion and Surface Expression of Intercellular Adhesion Molecule-1 on Endothelial Cells

Circulation ◽

10.1161/01.cir.98.12.1164 ◽

1998 ◽

Vol 98 (12) ◽

pp. 1164-1171 ◽

Cited By ~ 155

Author(s):

Meinrad Gawaz ◽

Franz-Josef Neumann ◽

Timm Dickfeld ◽

Werner Koch ◽

Karl-Ludwig Laugwitz ◽

...

Keyword(s):

Endothelial Cells ◽

Adhesion Molecule ◽

Surface Expression ◽

Intercellular Adhesion ◽

Intercellular Adhesion Molecule ◽

Intercellular Adhesion Molecule 1 ◽

Monocyte Chemotactic Protein ◽

Activated Platelets ◽

Chemotactic Protein

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HDL-Mediated Lipid Influx to Endothelial Cells Contributes to Regulating Intercellular Adhesion Molecule (ICAM)-1 Expression and eNOS Phosphorylation

International Journal of Molecular Sciences ◽

10.3390/ijms19113394 ◽

2018 ◽

Vol 19 (11) ◽

pp. 3394 ◽

Cited By ~ 6

Author(s):

Mónica Muñoz-Vega ◽

Felipe Massó ◽

Araceli Páez ◽

Gilberto Vargas-Alarcón ◽

Ramón Coral-Vázquez ◽

...

Keyword(s):

Endothelial Cells ◽

Adhesion Molecule ◽

Hdl Cholesterol ◽

Intercellular Adhesion ◽

Intercellular Adhesion Molecule ◽

High Density Lipoproteins ◽

Type I ◽

Intercellular Adhesion Molecule 1 ◽

Apo Ai

Reverse cholesterol transport (RCT) is considered as the most important antiatherogenic role of high-density lipoproteins (HDL), but interventions based on RCT have failed to reduce the risk of coronary heart disease. In contrast to RCT, important evidence suggests that HDL deliver lipids to peripheral cells. Therefore, in this paper, we investigated whether HDL could improve endothelial function by delivering lipids to the cells. Internalization kinetics using cholesterol and apolipoprotein (apo) AI fluorescent double-labeled reconstituted HDL (rHDL), and human dermal microvascular endothelial cells-1 (HMEC-1) showed a fast cholesterol influx (10 min) and a slower HDL protein internalization as determined by confocal microscopy and flow cytometry. Sphingomyelin kinetics overlapped that of apo AI, indicating that only cholesterol became dissociated from rHDL during internalization. rHDL apo AI internalization was scavenger receptor class B type I (SR-BI)-dependent, whereas HDL cholesterol influx was independent of SR-BI and was not completely inhibited by the presence of low-density lipoproteins (LDL). HDL sphingomyelin was fundamental for intercellular adhesion molecule-1 (ICAM-1) downregulation in HMEC-1. However, vascular cell adhesion protein-1 (VCAM-1) was not inhibited by rHDL, suggesting that components such as apolipoproteins other than apo AI participate in HDL’s regulation of this adhesion molecule. rHDL also induced endothelial nitric oxide synthase eNOS S1177 phosphorylation in HMEC-1 but only when the particle contained sphingomyelin. In conclusion, the internalization of HDL implies the dissociation of lipoprotein components and a SR-BI-independent fast delivery of cholesterol to endothelial cells. HDL internalization had functional implications that were mainly dependent on sphingomyelin. These results suggest a new role of HDL as lipid vectors to the cells, which could be congruent with the antiatherogenic properties of these lipoproteins.

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