Age‐Related Decline in Murine Macrophage Production of Nitric Oxide

Abstract

Since certain functions mediated by nitric oxide (NO) decline with age, the age dependence of NO production by macrophages from BALB/c mice was investigated. Lipopolysaccharide-, peptidoglycan-polysaccharide-, or interferon-gamma-stimulated splenic and peritoneal macrophages from young (1 month old), middle-aged (4-5 months old), and old (6-20 months old) BALB/c mice showed a progressive and marked decline in NO production. This age-related decline in inducible NO extended to C57/BL6 and CB6F1 mice. mRNA for inducible NO synthase (iNOS), the enzyme responsible for inducible NO production by macrophages, also declined with age. Importantly, the reduced NO production by macrophages from old mice could be up-regulated by pretreating the mice with either cholera toxin or concanavalin A. These findings indicate that reduced production of NO by murine macrophages correlates directly with advancing age, likely due to deficient signals or signal transduction responsible for iNOS mRNA and protein generation.

Nitric Oxide in Malaria

“…These observations may be related to age-related difference in NO production (Kissin et al, 1997;Tsukahara et al, 1997;Anstey et al, 1999b). Our recent studies in Tanzanian children show that NO production is highest in infancy, falling after the first year of life, then rising again after 5 years of age (Anstey et al, 1999b).…”

Age-related changes in immunity: implications for vaccination in the elderly

“…23). An overwhelming body of evidence indicates that, similar to granulocytes, ageing macrophages have an impaired respiratory burst and a reduced capacity to produce superoxide anion and nitric oxide ( Refs 24,25,26). They are also unable to upregulate the expression of major histocompatibility complex (MHC) class II, thus impairing their capacity to present antigen and to trigger CD4 þ T-cell responses (Ref.…”

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].…”

“…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]. An age-related reduced ability to produce NO and kill tumor cells has been described for resident peritoneal macrophages stimulated with IFN-g and LPS [12].…”