ASSOCIATIONS BETWEEN TGF-BETA-1 RECEPTORS IN HUMAN BONE-MARROW STROMAL CELLS

Bone marrow stromal cells are required for sustained haemopoiesis. Tra nsforming growth factor-beta (TGF-beta) is a multifunctional cytokine present in the bone marrow microenvironment which regulates the expres sion of several cytokines, cytokine receptors and cell adhesion elemen ts. The TGF-beta receptors type I and II, and endoglin, mediate TGF-be ta 1 binding to the membrane of human bone marrow stromal cells. [I-12 5]TGF-beta 1-affinity labelling experiments showed that three differen t anti-endoglin monoclonal antibodies co-immunoprecipitated a 68 kD TG F-beta 1-labelled polypeptide together with TGF-beta 1/endoglin comple xes. Here, we have shown that the 68 kD receptor corresponds to the ty pe I receptor, indicating that endoglin and the type I receptor associ ate on the membrane of these cells upon ligand binding. The expression of endoglin by stromal cells was found to be up-regulated by TGF-beta 1, but not by IL-1 beta. The association of endoglin with signalling components of the TGF-beta receptor system on the membrane of bone mar row stromal cells might modulate TGF-beta 1 access to the signalling p athways, and therefore it could regulate TGF-beta 1-mediated stromal c ellular responses.