Adenosine A2(A) receptor modulates the oxidative stress response of primed polymorphonuclear leukocytes after parabolic flight.
Hum Immunol
; 72(7): 547-52, 2011 Jul.
Article
em En
| MEDLINE
| ID: mdl-21513753
ABSTRACT
Space flight and gravitational stress can alter innate immune function. Parabolic flights (PFs) as a model for short-term gravitational changes prime the cytotoxic capability of polymorphonuclear leukocytes (PMNs). In view of the emerging role of adenosine in the regulation of innate immune responses, we examined the potency of adenosine to control the release of cytotoxic H(2)O(2) by primed PMNs via the adenosine receptor system. During PFs, microgravity conditions (<10(-2) G) are generated for approximately 22 seconds, followed by a hypergravity (1.8 G) phase resulting in gravitational stress. We studied the ex vivo effects of adenosine on the production of H(2)O(2) by stimulated PMNs and determined adenosine plasma levels and adenosine A2(A) receptor transcripts of leukocytes of PF participants (n = 15). Increasing concentrations of adenosine dose dependently reduced tissue-toxic H(2)O(2) production by PMNs with a half-maximal inhibitory concentration (IC(50)) of 19.5 nM before takeoff and 7.6 nM at 48 hours after PF. This increase in the adenosine-mediated inhibition of PMNs' H(2)O(2) production was completely reversed by addition of the A2(A) receptor antagonist ZM241385. PF induced a nonsignificant elevation in adenosine plasma levels; A2(A) receptor mRNA from leukocytes remained almost unchanged. Adenosine limits the oxidative stress response of PMNs after PFs through an upregulation of the adenosine A2(A) receptor function. This stop signal on inflammation is stronger than that under normal physiologic states and may limit further cytotoxic damage. Pharmacologic manipulation of the adenosine A2(A) receptor pathway could be a potential target for control of unwanted exacerbations of cytotoxic PMN functions.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vasodilatadores
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Adenosina
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Estresse Oxidativo
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Gravidade Alterada
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Receptores A2 de Adenosina
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Neutrófilos
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Humans
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Male
Idioma:
En
Revista:
Hum Immunol
Ano de publicação:
2011
Tipo de documento:
Article