Age-related decline of the acute local inflammation response: a mitigating role for the adenosine A2A receptor

• Published in: Aging (Albany, NY.) NY.), 2017-10, Vol.9 (10), p.2083-2097
• Main Authors: Laflamme, Cynthia, Mailhot, Geneviève Bertheau, Pouliot, Marc
• Format: Article
• Language: English
• Subjects: Research Paper
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.101303

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-1∝ 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.