Regulation of mouse bone marrow macrophage mannose receptor expression and activation by prostaglandin E and IFN-gamma.
The macrophage mannose receptor mediates the clearance of microorganisms and glycoproteins containing terminal mannose oligosaccharides. Cell surface expression of this receptor progresses with macrophage differentiation, and thus may be critical to the scavenger function of tissue and circulating macrophages. Bone marrow macrophages, which were used in this study, differentiate in culture and express functional mannose receptors. The cytokine IFN-gamma triggered activation of these macrophages and down-regulated cell surface expression of the mannose receptor after 48 h. Macrophage activation, as assessed by the generation of superoxide radicals, was inversely correlated with mannose receptor expression. The number of surface receptors was diminished by exposure to IFN-gamma, whereas the binding affinity of the mannose receptor remained unchanged. Treatment with IFN-gamma reduced receptor biosynthesis yet did not alter receptor degradation. Mannose receptor biosynthesis is up-regulated by PG of the E series, and these anti-inflammatory agents reversed the effects of IFN-gamma on receptor expression. Down-regulation of the mannose receptor by IFN-gamma was fully reversible by PGE, indicating that receptor levels are dependent on the functional state of the cell rather than being linked to terminal cell differentiation. The regulation of the receptor by cytokines and anti-inflammatory reagents suggests that the mannose receptor plays a critical role in macrophage scavenger functions and potentially in modulating inflammatory reactions.
Schreiber
S
S
Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO 63110.
Perkins
S L
SL
Teitelbaum
S L
SL
Chappel
J
J
Stahl
P D
PD
Blum
J S
JS
D000818:Animals; D001854:Bone Marrow Cells; D002455:Cell Division; D002478:Cells, Cultured; D007371:Interferon-gamma / Q000494:pharmacology*; D037181:Lectins, C-Type; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000737:chemistry*; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D051379:Mice; D008809:Mice, Inbred C3H; D011458:Prostaglandins E / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism
D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011458:Prostaglandins E; D011956:Receptors, Cell Surface; D007371:Interferon-gamma