Characterization of TGF-beta 1-binding proteins in human bone marrow stromal cells

The proliferation and differentiation of haemopoietic progenitor cells is dependent on their close relation with bone marrow stromal cells, which constitute a source of cytokines as well as expressing receptors for both the cytokines and progenitor cell adhesion molecules necessary for regulated haemopoiesis. We have generated human bone marrow stromal cell cultures and analysed the TGF-beta 1 receptor components expressed by these cells. [125I]TGF-beta 1-affinity labelling experiments showed the involvement of type I and II receptors in the binding of TGF-beta 1, as demonstrated by specific immunoprecipitation of [125I]TGF-beta 1-receptor complexes. In addition, large TGF-beta 1-labelled complexes displaying an electrophoretic mobility similar to betaglycan were also observed in these experiments. Endoglin, another component of the TGF-beta receptor system, was detected by flow cytometry on the surface of cultured marrow stromal cells, and in the human bone marrow stromal cell line Str-5, and was immunoprecipitated from surface-iodinated cells. Endoglin on the stromal cells was able to bind TGF-beta 1, as demonstrated by specific immunoprecipitation of [125I]TGF-beta 1-endoglin complexes using anti-endoglin antibodies. The results presented provide evidence that bone marrow stromal cells are fully capable of responding to TGF-beta 1. Given the important role of TGF-beta as a regulator of the synthesis of cytokines and cytokine receptors, as well as cell adhesion molecules, these data indicate that the binding of TGF-beta 1 by stromal cells might represent an important step in the regulation of the proliferation and differentiation of haemopoietic progenitor cells.