Interleukin-4 enhances murine bone marrow macrophage M-CSF receptor expression by a posttranscriptional mechanism.
Activated T-lymphocytes secrete interleukin-4 (IL-4), which has been shown to modulate a variety of monocyte activities requiring monocyte/macrophage colony-stimulating factor (M-CSF). To account for this interaction, we postulated that IL-4 acts on target cells by altering the expression of the M-CSF receptor (M-CSFr). To test this hypothesis, murine bone marrow macrophages were cultured under conditions that down-regulate M-CSFr and the effect of IL-4 on the reexpression of the receptor measured by binding of 125I-labeled M-CSF to the cells. The data show that incubation with IL-4 results in a dose-dependent, 2-3 x increase in M-CSFr with no change in binding affinity and a maximal effect on binding at about 12 h. This increase in M-CSFr is dependent upon new, specific protein synthesis as shown by the inhibitory action of cycloheximide, and gel analysis of radiolabeled, specific protein, immunoprecipitated with anti-M-CSFr antibody. Treatment with IL-4 does not stimulate M-CSFr mRNA expression but, consistent with enhanced receptor levels, does result in a heightened proliferative response to M-CSF. Thus, IL-4 affects M-CSF treated monocytic cells, at least in part, by altering the expression of M-CSFr.
Gibbons
R
R
Department of Growth and Development, University of California Medical Center, San Francisco 94143.
Ross
F P
FP
Perkins
S L
SL
Lacey
D L
DL
Martin
J
J
Ebner
R
R
Teitelbaum
S L
SL
Kahn
A J
AJ
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor; D004247:DNA; D003513:Cycloheximide; D016186:Receptor, Macrophage Colony-Stimulating Factor