Adenosine A2a receptors induce heterologous desensitization of chemokine   receptors

doi:10.1182/blood-2005-06-2599

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	Adenosine A2a receptors induce heterologous desensitization of chemokine receptors
	Zhang, N ; Yang, D ; Dong, HF ; Chen, Q ; Dimitrova, DI ; Rogers, TJ ; Sitkovsky, M ; Oppenheim, JJ
刊名	blood
	2006
关键词	STIMULATED HUMAN-NEUTROPHILS CROSS-DESENSITIZATION OPIOID RECEPTORS DENDRITIC CELLS DOWN-REGULATION MIP-1 ALPHA EXPRESSION PROTEIN CCR5 BETA
DOI	10.1182/blood-2005-06-2599
英文摘要	Adenosine, released by cells in an injurious or hypoxic environment, possesses potent anti-inflammatory effects by inhibiting the production of proinflammatory cytokines and superoxide anions (O-2(-)). We hypothesized that adenosine compounds also induced heterologous desensitization of chemokine receptors, which played a critical role in leukocyte trafficking. Our studies using adenosine receptor subtype-specific agonists revealed that pretreatment with adenosine compounds suppressed RANTES-induced chemotaxis and Ca2+ flux through activation of A2a adenosine receptor. Adenosine compounds also desensitized IL-8- and MCP-1-induced chemotaxis, but not that induced by fMLP. Activation of protein kinase A (PKA), a component of the signaling pathway induced by the A2a receptor, was sufficient to desensitize RANTES-induced chemotaxis. Inhibition of PKA reversed the desensitization effects of adenosine compounds, suggesting that PKA was necessary for A2a receptor-mediated heterologous desensitization. In a mouse model, prior activation of A2a receptors blocked RANTES-induced recruitment of leukocytes in an air pouch. Moreover, the A2a receptor-induced cross-desensitization also reduced the susceptibility of monocytes to infection by an R5 strain of HIV-1. Our results suggest that activation of A2a adenosine receptors suppresses chemokine receptor function, and such receptor cross-talk was based on the simple mechanism of PKA-mediated heterologous desensitization, thus contributing to the anti-inflammatory activity of adenosine.; Hematology; SCI(E); 0; ARTICLE; 1; 38-44; 108
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/398571]
专题	化学与分子工程学院
推荐引用方式 GB/T 7714	Zhang, N,Yang, D,Dong, HF,et al. Adenosine A2a receptors induce heterologous desensitization of chemokine receptors[J]. blood,2006.
APA	Zhang, N.,Yang, D.,Dong, HF.,Chen, Q.,Dimitrova, DI.,...&Oppenheim, JJ.(2006).Adenosine A2a receptors induce heterologous desensitization of chemokine receptors.blood.
MLA	Zhang, N,et al."Adenosine A2a receptors induce heterologous desensitization of chemokine receptors".blood (2006).