Immunomodulatory impact of the A2A adenosine receptor on the profile of chemokines produced by neutrophils
Immunomodulatory impact of the A2A adenosine receptor on the profile of chemokines produced by neutrophils
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DOI：
10.1096/fj.05-4804fje
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发表时间：
2005-11-01
期刊：
影响因子：
4.8
通讯作者：
Pouliot, M
中科院分区：
文献类型：
--
作者：
McColl, SR;St-Onge, M;Pouliot, M
在lps刺激的人中性粒细胞中，腺苷A（2A）受体的参与选择性地阻止了tnf - α、MIP-1 α /CCL3、MIP-1 β /CCL4、MIP-2 α /CXCL2和MIP-3 α /CCL20的表达和释放。在缺乏A（2A）受体的小鼠中，LPS注射后4小时迁移到气囊中的粒细胞表达的tnf - α、MIP-1 α和MIP-1 β mRNA水平高于野生型小鼠的pmn。注射LPS 72 h后，在A(2A)R敲除小鼠的气袋中存在的单核细胞中，IL-1 β、tnf - α、IL- 6和MCP-2/CCL6的表达较高。除了强调中性粒细胞是介导腺苷抗炎活性的早期和关键靶点外，这些结果还确定tnf - α和MIP趋化因子家族是基因产物，其表达受lps激活的PMNs中A(2A)R的激活的关键影响。因此，A(2A)R对PMNs产生炎症信号的调节可能通过降低炎症细胞的激活状态来影响炎症反应的演变。
In LPS-stimulated human neutrophils, engagement of the adenosine A(2A) receptor selectively prevented the expression and release of TNF-alpha, MIP-1 alpha/CCL3, MIP-1 beta/CCL4, MIP-2 alpha/CXCL2, and MIP-3 alpha/CCL20. In mice lacking the A(2A) receptor, granulocytes that migrated into the air pouch 4 h after LPS injection expressed higher mRNA levels of TNF-alpha, MIP-1 alpha, and MIP-1 beta than PMNs from wild-type mice. In mononuclear cells present in the air pouch 72 h after LPS injection, expression of IL-1 beta, TNF-alpha, IL- 6, and MCP-2/CCL6 was higher in A(2A)R knockout mice. In addition to highlighting neutrophils as an early and pivotal target for mediating adenosine anti-inflammatory activities, these results identify TNF-alpha and the MIP chemokine family as gene products whose expression is pivotally affected by activation of A(2A)R in LPS-activated PMNs. Modulation by A(2A)R in the production of inflammatory signals by PMNs may thus influence the evolution of an inflammatory response by reducing the activation status of inflammatory cells.