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Immunomodulatory impact of the A 2A adenosine receptor on the profile of chemokines produced by neutrophils
Author(s) -
McColl Shaun R.,
StOnge Mireille,
Dussault AndréeAnne,
Laflamme Cynthia,
Bouchard Line,
Boulanger Jean,
Pouliot Marc
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-4804fje
Subject(s) - cxcl2 , chemokine , adenosine , adenosine a2a receptor , ccl20 , chemistry , inflammation , receptor , chemotaxis , adenosine receptor , immunology , biology , chemokine receptor , biochemistry , agonist
In LPS‐stimulated human neutrophils, engagement of the adenosine A2A receptor selectively prevented the expression and release of TNF‐α, MIP‐1α/CCL3, MIP‐1β/CCL4, MIP‐2α/CXCl 2 , and MIP‐3α/CCl 2 0. In mice lacking the A2A receptor, granulocytes that migrated into the air pouch 4 h after LPS injection expressed higher mRNA levels of TNF‐α, MIP‐1α, and MIP‐1β than PMNs from wild‐type mice. In mononuclear cells present in the air pouch 72 h after LPS injection, expression of IL‐1β, TNF‐α, IL‐6, and MCP‐2/CCL6 was higher in A2AR knockout mice. In addition to highlighting neutrophils as an early and pivotal target for mediating adenosine anti‐inflammatory activities, these results identify TNF‐α and the MIP chemokine family as gene products whose expression is pivotally affected by activation of A2AR in LPS‐activated PMNs. Modulation by A2AR 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.