Adenosine A2A receptor modulates the oxidative stress response of primed polymorphonuclear leukocytes after parabolic flight

作者: Ines Kaufmann , Matthias Feuerecker , Alex Salam , Gustav Schelling , Manfred Thiel

DOI: 10.1016/J.HUMIMM.2011.03.021

关键词:

摘要: Abstract Space flight and gravitational stress can alter innate immune function. Parabolic flights (PFs) as a model for short-term changes prime the cytotoxic capability of polymorphonuclear leukocytes (PMNs). In view emerging role adenosine in regulation responses, we examined potency to control release H 2 O by primed PMNs via receptor system. During PFs, microgravity conditions ( −2 G) are generated approximately 22 seconds, followed hypergravity (1.8 phase resulting stress. We studied ex vivo effects on production stimulated determined plasma levels A2 A transcripts PF participants n = 15). Increasing concentrations dose dependently reduced tissue-toxic with half-maximal inhibitory concentration (IC 50 ) 19.5 nM before takeoff 7.6 at 48 hours after PF. This increase adenosine-mediated inhibition PMNs' was completely reversed addition antagonist ZM241385. induced nonsignificant elevation levels; mRNA from remained almost unchanged. Adenosine limits oxidative response PFs through an upregulation stop signal inflammation is stronger than that under normal physiologic states may limit further damage. Pharmacologic manipulation pathway could be potential target unwanted exacerbations PMN functions.

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