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

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.