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Loss of ATP diphosphohydrolase activity with endothelial cell activation.

Robson SC, Kaczmarek E, Siegel JB, Candinas D, Koziak K, Millan M, Hancock WW, Bach FH - J. Exp. Med. (1997)

Bottom Line: This latter effect is mediated in a number of ways, including expression by EC of thrombomodulin and heparan sulfate, both of which are lost from the EC surface as part of the activation response to proinflammatory cytokines.Loss of these anticoagulant molecules potentiates the procoagulant properties of the injured vasculature.We describe here that the antithrombotic effects of the ATPDase, like heparan sulfate and thrombomodulin, are lost after EC activation, both in vitro and in vivo.

View Article: PubMed Central - PubMed

Affiliation: Sandoz Center for Immunobiology, Boston, Massachusetts, USA.

ABSTRACT
Quiescent endothelial cells (EC) regulate blood flow and prevent intravascular thrombosis. This latter effect is mediated in a number of ways, including expression by EC of thrombomodulin and heparan sulfate, both of which are lost from the EC surface as part of the activation response to proinflammatory cytokines. Loss of these anticoagulant molecules potentiates the procoagulant properties of the injured vasculature. An additional thromboregulatory factor, ATP diphosphohydrolase (ATPDase; designated as EC 3.6.1.5) is also expressed by quiescent EC, and has the capacity to degrade the extracellular inflammatory mediators ATP and ADP to AMP, thereby inhibiting platelet activation and modulating vascular thrombosis. We describe here that the antithrombotic effects of the ATPDase, like heparan sulfate and thrombomodulin, are lost after EC activation, both in vitro and in vivo. Because platelet activation and aggregation are important components of the hemostatic changes that accompany inflammatory diseases, we suggest that the loss of vascular ATPDase may be crucial for the progression of vascular injury.

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Hydrolysis of [14C]ADP to AMP by EC-associated ATPDase. Radiolabeled ADP hydrolysis to AMP, and consequent catalysis to  adenosine by pEC, was measured by TLC of supernatants from EC cultures. ADP was rapidly degraded and the radio-label appeared as AMP  initially, and then adenosine over a time period of 30 min.
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Figure 2: Hydrolysis of [14C]ADP to AMP by EC-associated ATPDase. Radiolabeled ADP hydrolysis to AMP, and consequent catalysis to adenosine by pEC, was measured by TLC of supernatants from EC cultures. ADP was rapidly degraded and the radio-label appeared as AMP initially, and then adenosine over a time period of 30 min.

Mentions: The hydrolysis of radiolabeled ADP to AMP and consequent catalysis to adenosine by confluent, intact pEC was measured by TLC. ADP was rapidly degraded by the ectoenzyme associated with EC. AMP, and then adenosine, were generated during 30 min incubation with dipyridamole (10 μM; Fig. 2). Adenosine appearance was probably associated with 5′ nucleotidase activity (Fig. 2). These kinetic determinations were in concordance with those stated for the pEC ecto-enzyme as determined by another methodology (39).


Loss of ATP diphosphohydrolase activity with endothelial cell activation.

Robson SC, Kaczmarek E, Siegel JB, Candinas D, Koziak K, Millan M, Hancock WW, Bach FH - J. Exp. Med. (1997)

Hydrolysis of [14C]ADP to AMP by EC-associated ATPDase. Radiolabeled ADP hydrolysis to AMP, and consequent catalysis to  adenosine by pEC, was measured by TLC of supernatants from EC cultures. ADP was rapidly degraded and the radio-label appeared as AMP  initially, and then adenosine over a time period of 30 min.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196106&req=5

Figure 2: Hydrolysis of [14C]ADP to AMP by EC-associated ATPDase. Radiolabeled ADP hydrolysis to AMP, and consequent catalysis to adenosine by pEC, was measured by TLC of supernatants from EC cultures. ADP was rapidly degraded and the radio-label appeared as AMP initially, and then adenosine over a time period of 30 min.
Mentions: The hydrolysis of radiolabeled ADP to AMP and consequent catalysis to adenosine by confluent, intact pEC was measured by TLC. ADP was rapidly degraded by the ectoenzyme associated with EC. AMP, and then adenosine, were generated during 30 min incubation with dipyridamole (10 μM; Fig. 2). Adenosine appearance was probably associated with 5′ nucleotidase activity (Fig. 2). These kinetic determinations were in concordance with those stated for the pEC ecto-enzyme as determined by another methodology (39).

Bottom Line: This latter effect is mediated in a number of ways, including expression by EC of thrombomodulin and heparan sulfate, both of which are lost from the EC surface as part of the activation response to proinflammatory cytokines.Loss of these anticoagulant molecules potentiates the procoagulant properties of the injured vasculature.We describe here that the antithrombotic effects of the ATPDase, like heparan sulfate and thrombomodulin, are lost after EC activation, both in vitro and in vivo.

View Article: PubMed Central - PubMed

Affiliation: Sandoz Center for Immunobiology, Boston, Massachusetts, USA.

ABSTRACT
Quiescent endothelial cells (EC) regulate blood flow and prevent intravascular thrombosis. This latter effect is mediated in a number of ways, including expression by EC of thrombomodulin and heparan sulfate, both of which are lost from the EC surface as part of the activation response to proinflammatory cytokines. Loss of these anticoagulant molecules potentiates the procoagulant properties of the injured vasculature. An additional thromboregulatory factor, ATP diphosphohydrolase (ATPDase; designated as EC 3.6.1.5) is also expressed by quiescent EC, and has the capacity to degrade the extracellular inflammatory mediators ATP and ADP to AMP, thereby inhibiting platelet activation and modulating vascular thrombosis. We describe here that the antithrombotic effects of the ATPDase, like heparan sulfate and thrombomodulin, are lost after EC activation, both in vitro and in vivo. Because platelet activation and aggregation are important components of the hemostatic changes that accompany inflammatory diseases, we suggest that the loss of vascular ATPDase may be crucial for the progression of vascular injury.

Show MeSH
Related in: MedlinePlus