title: Role of ATP in trauma-associated cytokine release and apoptosis by P2X7 ion channel stimulation.
abstract: 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.
authors: Sektion Experimentelle Anaesthesiologie, Department of Clinical Anesthesiology, Universitaetsklinikum Ulm, Steinhoevelstrasse 9, 89075 Ulm, Germany. marion.schneider@uni-ulm.de
authors: E Marion
authors: EM
authors: Schneider
authors: Katrin
authors: K
authors: Vorlaender
authors: Xueling
authors: X
authors: Ma
authors: Weidong
authors: W
authors: Du
authors: Manfred
authors: M
authors: Weiss
mesh_terms: 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
chemical_list: D016207:Cytokines; D007473:Ion Channels; C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate