Macrophage-colony-stimulating factor regulates expression of the integrins α4β1 and α5β1 by murine bone marrow macrophages

M. Shima, S. L. Teitelbaum, V. M. Holers, C. Ruzicka, P. Osmack, F. P. Ross

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We observed that when monocyte/macrophage precursors derived from routine 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 α4β1 and/or α5β1 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 β1 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 α4β1 and α5β1, leading to interactions with components of the marrow microenvironment necessary for cell maturation.

Original languageEnglish
Pages (from-to)5179-5183
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number11
StatePublished - Jun 22 1995


  • cytokines
  • hematopoiesis
  • stromal matrix

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