Role of ATP in trauma-associated cytokine release and apoptosis by P2X7 ion channel stimulation.
Trauma causes immediate cytokine release and the systemic inflammatory response syndrome (SIRS), often preceding sepsis and septic shock. Mechanisms may involve P2X7 ion channel activation via adenosine 5'-triphosphate (ATP) released from surrounding tissue and platelets. A number of single nucleotide polymorphisms (SNPs) influence the nature and magnitude of P2X7-stimulated cytokine release and apoptosis. In whole blood and isolated mononuclear blood cells (PBMCs) of donors with wild-type and heterozygous mutated genotypes, we found downregulated IL-8 and caspase-3 activation but no reproducible effect on tumor necrosis factor (TNF)-alpha and IL-1beta release. IL-8 and caspase-3 activation were both influenced by paxilline, an inhibitor of calcium-activated potassium channels. Confocal laser scanning microscopy demonstrated that calcium signaling is affected by paxilline as well. We propose that blockade of potassium channels may be relevant to attenuate ATP-induced cytokine responses and apoptosis. The presence of functional SNPs in heterozygous genotypes appears to play a role.
Schneider
E Marion
EM
Sektion Experimentelle Anaesthesiologie, Department of Clinical Anesthesiology, Universitaetsklinikum Ulm, Steinhoevelstrasse 9, 89075 Ulm, Germany. marion.schneider@uni-ulm.de
Vorlaender
Katrin
K
Ma
Xueling
X
Du
Weidong
W
Weiss
Manfred
M
D000255:Adenosine Triphosphate / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058486:Receptors, Purinergic P2X7; D014947:Wounds and Injuries / Q000378:metabolism* / Q000503:physiopathology
D016207:Cytokines; D007473:Ion Channels; C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate