Human macrophage activation. Modulation of mannosyl, fucosyl receptor activity in vitro by lymphokines, gamma and alpha interferons, and dexamethasone

Abstract

We describe a sensitive assay to measure immune activation of human macrophages in cell culture. Freshly isolated blood monocytes from normal subjects lack the ability to endocytose and degrade mannosyl-terminated glycoconjugates via specific receptors, but acquired this activity after cultivation in autologous serum for ~3 d. Addition of specific antigen, purified protein derivative, or T cell mitogens to mononuclear cells prevented the appearance of macrophage mannosyl receptor activity and lymphokine, γ-, and α-interferons selectively down-regulated receptor activity in monocyte-macrophage targets. The effects of antigen challenge and γ-interferon on mannosyl receptors can be prevented by 10-8 M dexamethasone. Dexamethasone also inhibited release of another macrophage activation marker, plasminogen activator, which was increased by both γ- and α-interferons. These studies show that activation of human macrophages is regulated by opposing actions of lymphokines and glucocorticoids.