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Original

ATP inhibits hydroxyl radical formation and the inflammatory response of stimulated whole blood even under circumstances of severe oxidative stress

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Pages 53-58 | Received 30 Jun 2005, Published online: 07 Jul 2009
 

Abstract

We recently reported that Adenosine-5′-triphosphate (ATP) is able to inhibit the inflammatory reaction in stimulated whole blood. Many diseases, in which inflammatory reactions are involved, are associated with oxidative stress. In the present study, we therefore, investigated the effect of ATP on cytokine release in stimulated whole blood under conditions of oxidative stress, as simulated by pre-incubation of blood with hydrogen peroxide (H2O2). In the presence of H2O2, ATP at concentrations of 100 and 300 μM inhibited Tumour Necrosis factor-alpha (TNF-α) release and stimulated IL-10 release in LPS-PHA stimulated whole blood. Moreover, electron spin resonance (ESR) measurements showed that ATP and its breakdown product Adenosine-5′-diphosphate (ADP) attenuated spin trap-hydroxyl radical adduct formation in the Fenton reaction. Our results demonstrate that even in circumstances of severe oxidative stress, ATP has marked anti-inflammatory properties in stimulated whole blood. Moreover, the inhibition of the hydroxyl radical ESR signal indicates a direct attenuation of oxidative stress by ATP.

Abbreviations
ADP=

Adenosine-5′-diphosphate

AMP=

Adenosine-5′-monophosphate

ATP=

Adenosine-5′-triphosphate

COPD=

Chronic obstructive pulmonary disease

DMPO=

5,5-dimethyl-1-pyrroline N-oxide

ESR=

Electron spin resonance spectroscopy

H2O2=

Hydrogen peroxide

IL-10=

Interleukin-10

IL-6=

Interleukin-6

LPS=

Lipopolysaccharide

NFκB=

Nuclear factor-kappaB

√OH=

Hydroxyl radical

PHA=

Phytohemagglutinin

ROS=

Reactive oxygen species

SEM=

Standard error mean

TLR-4=

Toll-like receptor 4

TNF-α=

Tumor necrosis factor-alpha

Abbreviations
ADP=

Adenosine-5′-diphosphate

AMP=

Adenosine-5′-monophosphate

ATP=

Adenosine-5′-triphosphate

COPD=

Chronic obstructive pulmonary disease

DMPO=

5,5-dimethyl-1-pyrroline N-oxide

ESR=

Electron spin resonance spectroscopy

H2O2=

Hydrogen peroxide

IL-10=

Interleukin-10

IL-6=

Interleukin-6

LPS=

Lipopolysaccharide

NFκB=

Nuclear factor-kappaB

√OH=

Hydroxyl radical

PHA=

Phytohemagglutinin

ROS=

Reactive oxygen species

SEM=

Standard error mean

TLR-4=

Toll-like receptor 4

TNF-α=

Tumor necrosis factor-alpha

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