Age‐dependent change in reactive oxygen species and nitric oxide generation by rat alveolar macrophages*

Abstract

SummaryImmunosenescence is an age-associated dysregulation of the immune function, which contributes to increased susceptibility to disease in the elderly. Alveolar macrophages (AM) are known phagocytes that generate reactive oxygen species (ROS) and nitric oxide (NO), essential mediators for host defence. We studied phagocytosis, ROS and NO production in AM obtained from young, adult and senescent rats (1-2, 9-12 and 18-24 months old, respectively) after exposure to lipopolysaccharide (LPS, 0.1-10 µ µ µ µ g mL), 12-O-tetradecanoylphorbol 13-acetate (TPA, 0.1 µ µ µ µ g mL − − − − 1 ) or LPS + TPA in culture. Phagocytosis was significantly lower in control AM from adult rats than in AM from young animals. Nevertheless, AM from adult animals pretreated with LPS exhibited higher phagocytic capacity than AM from younger animals. ROS was identified by the NBT test at single cell level and quantified by automated image analysis. When TPA was added to all three populations, AM from adult and senescent animals responded more than AM from young animals. All LPS-stimulated AM produce more NO than controls. However, NO production increased three-, four-and two-fold in young, adult and senescent animals, respectively. Our results demonstrate that AM from young, adult and senescent animals display differential responsiveness to inflammatory mediators. Therefore, aging processes markedly affect AM metabolic functions and may further compromise the lung immune defence response, increasing adverse long-term health effects.

Nutrition, diet and immunosenescence

“…The authors also showed that these polyphenols also influence B cell function and increase production of protective IgA and IgG. Based on the notion that polyphenols can partially restore the function of aged macrophages (Tasat et al, 2003) the authors speculated that moderate intake of red wine may be beneficial in ageing. Animal models of ageing have shown positive results with resveratrol, a polyphenol found in grape skins and berries, significantly increasing T helper cells in aged rats (Yuan et al, 2012) and that the phytochemical, Echinacea purpurea, can increase NK cell numbers in aged mice to levels observed in young adult mice, as well as significantly increasing NK cell cytolytic activity (Currier and Miller, 2000).…”

The aging innate immune system

“…Studies in rats have shown a 75% decrease in the ability of macrophages from aged animals to produce superoxide anion following incubation with IFN-g [15], a consequence of the reduced respiratory burst. Additionally, the generation of lipopolysaccharide (LPS)-stimulated reactive oxygen species (ROS) and nitric oxide (NO) is diminished in alveolar macrophages from aged rats [16,17]. Moreover, splenic and peritoneal macrophages from aged mice produce less NO and inducible NO synthase (iNOS) mRNA than young macrophages [17].…”

Analysis of factorial time-course microarrays with application to a clinical study of burn injury

“…Hypermetabolism and inflammation are two hallmarks of the body's response to burn injury (15,16). Our analysis reveals that significantly enriched pathways in C1 include glycosphingolipid biosynthesis-globoseries (5 genes, p value: 8.19E-5), primary immunodeficiency signaling (10 genes, p value: 0.001), keratan sulfate biosynthesis (5 genes, p value: 0.007), galactose metabolism (5 genes, p value: 0.01), ubiquinone biosynthesis (8 genes, p value: 0.01) , death receptor signaling (7 genes, p value: 0.01), and mitochondrial dysfunction (12 genes, p value: 0.01) (the p values are calculated from the hypergeometric test; see SI Text for the details of pathway analysis).…”

“…Finally, C4 genes are related only to age and not burn injury. It includes genes (RHOB, PPP1CA, and MAP2K7) involved in production of nitric oxide and reactive oxygen species in macrophage, which has been related to the aging process (15).…”