The effect of age and soluble mediators on macrophage function in vitro

Abstract

Macrophages from young (8-10 m·onths old) and old (22-24 . mon'ths old) F344 .rats were examined in_ vitro to determine whether macrophage function was compromised in old rats. Thioglycollateelicited macrophages were us~d. The inflammatory response in old . - rats yielded 75% fewer macrophages than_ young rats. However, age did not have any effect on the expression of alkaline phosphodiesterase I activity, which functions as a marker of. macrophage activation. Similarly, macrophages from old rats performed as well as macrophages from young rats in their ability to inhibit tumor cell growth in cytostasis assays using both ·rat.and mouse tumor cell lines. Yet macrophage function in vivo depends not only on intrinsic functional.ability but also upon environmental stimuli. Plasma fibronectin (Fn) increases in concentration during aging in many orga~sms, including Sprague-Dawley rats. Fn had a differential effect on marker ectoenzyme activities in the Sprague-Dawley --·model; it enhanced activation in young macrophages, while decreasing activation in old macrophages. In the cytostasis assay system, fibronectin enhanced cytostasis of . both young and old F344 macrophages, but the old macrophages were 30% less sensitive to Fn's effect. Macrophages from young and . old rats were equally responsive to the activating effects of lipopolysaccharide (LPS) in the cytostasis assay. Thus, whil~ some intrinsic macrophage functions are unimpaired during aging, macrophage function in vivo will be due to the complex environment of stimulatory and inhibitory signals in the aging environment.