Immunomodulatory impact of the A2A adenosine receptor on the profile of chemokines produced by neutrophils.
In LPS-stimulated human neutrophils, engagement of the adenosine A2A receptor selectively prevented the expression and release of TNF-alpha, MIP-1alpha/CCL3, MIP-1beta/CCL4, MIP-2alpha/CXCL2, and MIP-3alpha/CCL20. In mice lacking the A2A receptor, granulocytes that migrated into the air pouch 4 h after LPS injection expressed higher mRNA levels of TNF-alpha, MIP-1alpha, and MIP-1beta than PMNs from wild-type mice. In mononuclear cells present in the air pouch 72 h after LPS injection, expression of IL-1beta, TNF-alpha, 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-alpha 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.
McColl
Shaun R
SR
Centre de Recherche en Rhumatologie et Immunologie du CHUQ (CHUL), and Department of Anatomy-Physiology, Faculty of Medicine, Laval University, Quebec, Canada.
St-Onge
Mireille
M
Dussault
Andrée-Anne
AA
Laflamme
Cynthia
C
Bouchard
Line
L
Boulanger
Jean
J
Pouliot
Marc
M
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D018925:Chemokines / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D018925:Chemokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; D000241:Adenosine