Immunomodulatory impact of the A2A adenosine receptor on the profile of chemokines produced by neutrophils

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.