Open AccessAge-related decline of the acute local inflammation response: a mitigating role for the adenosine A2A receptor
Author(s) -
Christian Laflamme,
Geneviève Mailhot,
Marc Pouliot
Publication year - 2017
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.101303
Subject(s) - cxcl1 , inflammation , immunology , adenosine a2a receptor , cytokine , neutrophil elastase , elastase , receptor , knockout mouse , medicine , chemokine , endocrinology , biology , adenosine receptor , biochemistry , agonist , enzyme
Aging is accompanied by an increase in markers of innate immunity. How aging affects neutrophil functions remains of debate.The adenosine A 2A receptor (A 2A R), essential to the resolution of inflammation, modulates neutrophil functions. We sought to determine whether or not A 2A R protects against the effects of aging. We monitored neutrophil influx, viability, and activation as well as cytokine accumulation in wild-type (WT) and A 2A R-knockout mice (KO) at three different ages.Several readouts decreased with aging: neutrophil counts in dorsal air pouches (by up to 55%), neutrophil viability (by up to 56%), elastase and total protein in exudates (by up to 80%), and local levels of cytokines (by up to 90%). Each of these parameters was significantly more affected in A 2A R-KO mice. CXCL1-3 levels were largely unaffected. The effects of aging were not observed systemically. Preventing neutrophil influx into the air pouch caused a comparable cytokine pattern in young WT mice. Gene expression (mRNA) in leukocytes was affected, with CXCL1 and CCL4 increasing and with TNF and IL-1α decreasing. Conclusion Aging has deleterious effects on the acute inflammatory response and neutrophil-related activities, and defective migration appears as an important factor. A functional A 2A R signaling pathway delays some of these.