Interleukin-4 rapidly down-modulates the macrophage colony-stimulating factor receptor in murine macrophages.
The activation of macrophages interferes with their response to macrophage colony-stimulating factor (M-CSF), the main growth and differentiation factor for mononuclear phagocytes. We tested the rapid effects of interleukin-4 (IL-4), the alternative macrophage activator produced by Th2 helper lymphocytes, on the receptor for M-CSF (M-CSFR) expressed on the cell surface of murine macrophages. IL4 rapidly down-modulated M-CSFR in a dose-dependent fashion. This effect was unique to IL-4 among a number of Th2-produced cytokines, none of which, with the exception of IL4 itself, is able to activate macrophages. The down-modulation of M-CSFR by IL4 was partially prevented by the inhibition of the activity of phospholipase C or protein kinase C. The data are consistent with the hypothesis that the down-modulation of M-CSFR is a property common to, and exclusive of, macrophage activators, and is driven by different activators via a common mechanism.
Dello Sbarba
P
P
Istituto di Patologia Generale della Università degli Studi di Firenze, Florence, Italy.
Rovida
E
E
Caciagli
B
B
Nencioni
L
L
Labardi
D
D
Paccagnini
A
A
Savini
L
L
Cipolleschi
M G
MG
D000818:Animals; D002461:Cell Line, Transformed; D015536:Down-Regulation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D008222:Lymphokines / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D018418:Th2 Cells / Q000378:metabolism; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000502:physiology
D004791:Enzyme Inhibitors; D008222:Lymphokines; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor; D011493:Protein Kinase C; D010738:Type C Phospholipases