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, y-, and a-interferons selectively downregulated receptor activity in monocyte-macrophage targets. The effects of antigen challenge and y-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 'y-and a-interferons. These studies show that activation of human macrophages is regulated by opposing actions of lymphokines and glucocorticoids.

Regulation of mannose receptor synthesis and turnover in mouse J774 macrophages

“…In this respect, the receptor may function in the removal of these pathogens during the earliest stages of the immune response before macrophage activation. Modulation of mannose receptor activity has been observed in macrophages after differentiation and activation [12][13][14][15][16]. Our studies with J774 clones suggests that there may be two levels of regulation, one where receptor numbers are modulated by receptor synthesis and receptor degradation and a second where the intracellular itinerary of the receptor is modulated.…”

“…Activation of macrophages with pathogens [13] or lymphokines [14][15][16] down-regulates receptor activity. In contrast, dexamethasone [15,17], vitamin D 3 [18], prostaglandins [19], and interleukin-4 (IL-4) [20 and S. E. Pontow and P. D. Stahl, unpublished results] have been shown to increase mannose receptor activity. Expression of the receptor was assessed in each case by monitoring ligand binding and internalization.…”

Identification of a distinct glucocorticosteroid-insensitive pulmonary macrophage phenotype in patients with chronic obstructive pulmonary disease

“…These distinct macrophage 'activation' or 'polarization' states were first described almost four decades ago 10,11 and may reflect different macrophage phenotypes 12 . These phenotypes have been assigned M1 corresponding broadly to 'classically activated' and M2 corresponding to 'alternatively activated' 13 .…”

Characterization of a rat alveolar macrophage cell line that expresses a functional mannose receptor

“…Agents that inhibit proinflammatory activity of macrophages such as interleukin (IL)-4 [19] and dexamethasone [17,20] dramatically up-regulate MR activity, whereas treatment with macrophage-activating agents such as interferon-␥ (IFN-␥) decrease MR activity [6,[21][22][23]. Studies of the functional significance of this regulation have been hampered by the lack of a continuous macrophage cell line that expresses high levels of functional and regulated MR.…”