Age-related decline of the acute local inflammation response: a mitigating role for the adenosine A_2A receptor.

ABSTRACT: 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_2AR), essential to the resolution of inflammation, modulates neutrophil functions. We sought to determine whether or not A_2AR protects against the effects of aging. We monitored neutrophil influx, viability, and activation as well as cytokine accumulation in wild-type (WT) and A_2AR-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_2AR-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.ConclusionAging has deleterious effects on the acute inflammatory response and neutrophil-related activities, and defective migration appears as an important factor. A functional A_2AR signaling pathway delays some of these.

SUBMITTER: Laflamme C 

PROVIDER: S-EPMC5680557 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature