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 necessa ry for regulated haemopoiesis. We have generated human bone marrow str omal cell cultures and analysed the TGF-beta 1 receptor components exp ressed by these cells. [I-125]-TGF-beta 1-affinity labelling experimen ts showed the involvement of type I and II receptors in the binding of TGF-beta 1, as demonstrated by specific immunoprecipitation of [I-125 ]TGF-beta 1-receptor complexes. In addition, large TGF-beta 1-labelled complexes displaying an electrophoretic mobility similar to betaglyca n were also observed in these experiments. Endoglin, another component of the TGF-beta receptor system, was detected by now cytometry on the surface of cultured marrow stromal cells, and in the human bone marro w stromal cell line Str-5, and was immunoprecipitated from surface-iod inated cells, Endoglin on the stromal cells was able to bind TGF-beta 1, as demonstrated by specific immunoprecipitation of [I-125]TGF-beta 1-endoglin complexes using anti-endoglin antibodies. The results prese nted 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 w ell as cell adhesion molecules, these data indicate that the binding o f TGF-beta 1 by stromal cells might represent an important step in the regulation of the proliferation and differentiation of haemopoietic p rogenitor cells.