Physiological control of immune response and inflammatory tissue damage by hypoxia-inducible factors and adenosine A2A receptors

被引：586

作者：

Sitkovsky, MV ^{[1
]}

Lukashev, D ^{[1
]}

Apasov, S ^{[1
]}

Kojima, H ^{[1
]}

Koshiba, M ^{[1
]}

Caldwell, C ^{[1
]}

Ohta, A ^{[1
]}

Thiel, M ^{[1
]}

机构：

[1] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA

来源：

ANNUAL REVIEW OF IMMUNOLOGY | 2004年 / 22卷

关键词：

hypoxia; adenosine receptors; immunity; inflammation;

D O I：

10.1146/annurev.immunol.22.012703.104731

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Immune cell-mediated destruction of pathogens may result in excessive collateral damage to normal tissues, and the failure to control activated immune cells may cause inummopathologies. The search for physiological mechanisms that down-regulate activated immune cells has revealed a critical role for extracellular adenosine and for immuno suppressive A(2A) adenosine receptors in protecting tissue from inflammatory damage. Tissue damage-associated deep hypoxia, hypoxia-inducible factors, and hypoxia-induced accumulation of adenosine may represent one of the most fundamental and immediate tissue-protecting mechanisms, with adenosine A(2A) receptors triggering "OFF" signals in activated immune cells. In these regulatory mechanisms, oxygen deprivation and extracellular adenosine accumulation serve as "reporters," while A(2A) adenosine receptors serve as "sensors" of excessive tissue damage. The A(2A) receptor-triggered generation of intracellular cAMP then inhibits activated immune cells in a delayed negative feedback manner to prevent additional tissue damage. Targeting A(2A) adenosine receptors may have important clinical applications.

引用

页码：657 / 682

页数：26

共 120 条

[1] Aggravated brain damage after hypoxic ischemia in immature adenosine A2A knockout mice [J].