Macrophage-colony-stimulating factor regulates expression of the integrins alpha 4 beta 1 and alpha 5 beta 1 by murine bone marrow macrophages.
We observed that when monocyte/macrophage precursors derived from murine bone marrow were treated with macrophage-colony-stimulating factor (M-CSF), there was a dose-dependent increase in both the number of adherent cells and the degree to which the cells were highly spread. Attachment was supported by fibronectin, but not by vitronectin or laminin, suggesting that the integrins alpha 4 beta 1 and/or alpha 5 beta 1 might mediate this event. Binding to fibronectin was blocked partially by antibodies to either integrin, and inhibition was almost complete when the antibodies were used in combination. By a combination of surface labeling with 125I and metabolic labeling with [35S]methionine and [35S]cysteine, we demonstrated that M-CSF treatment led to increased synthesis and surface expression of the two beta 1 integrins. Since attachment to fibronectin and/or stromal cells plays an important role in the maturation of other hematopoietic lineages, we propose that the action of M-CSF in the differentiation of immature monocytes/macrophages includes stimulated expression of the integrins alpha 4 beta 1 and alpha 5 beta 1, leading to interactions with components of the marrow microenvironment necessary for cell maturation.
Shima
M
M
Department of Pathology, Jewish Hospital, Washington University Medical Center, St. Louis, MO 63110, USA.
Teitelbaum
S L
SL
Holers
V M
VM
Ruzicka
C
C
Osmack
P
P
Ross
F P
FP
D000818:Animals; D000906:Antibodies; D001345:Autoradiography; D001853:Bone Marrow / Q000378:metabolism*; D002448:Cell Adhesion; D002478:Cells, Cultured; D003545:Cysteine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005353:Fibronectins; D005786:Gene Expression Regulation / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D039041:Integrin alpha4beta1; D016023:Integrins / Q000096:biosynthesis* / Q000302:isolation & purification; D007797:Laminin; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008715:Methionine / Q000378:metabolism; D051379:Mice; D017469:Receptors, Fibronectin; D013462:Sulfur Radioisotopes
D000906:Antibodies; D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D007797:Laminin; D017469:Receptors, Fibronectin; D013462:Sulfur Radioisotopes; D016173:Macrophage Colony-Stimulating Factor; D008715:Methionine; D003545:Cysteine