Actions of molecules which regulate hemopoiesis on endothelial cells: memoirs of common ancestors?

ABSTRACT

The proliferation and differentiation of hematopoietic stem cells (hematopoiesis) takes place in close contact with stromal cells and matrix in bone marrow. Hematopoiesis requires cytokines, collectively termed colony stimulating factors (CSFs), which act on progenitor cell populations and induce their commitment to a specific lineage. For instance, leukemia, inhibitor factor and stem cell factor act on pluripotent cells and immature progenitors, granulocyte-macrophage colony stimulating factor (GM-CSF) acts at early stages of the development of myelomonocytic lineage, whereas granulocyte-colony stimulating factor (G-CSF) and macrophage-colony stimulating factor (M-CSF) act on more mature cells of the same lineage and are only required later during the differentiation of this cell lineage. A second important element for the hematopoietic process is the presence of extracellular matrix proteins, which bind CSFs and correctly present the molecules to specific receptors present on the surface of the progenitor cells. Finally, stromal cells (i.e. fibroblasts, endothelial cells and adipocytes) which support the growth of hematopoietic stem cells in vitro, are crucial for the production of CSFs and protein matrix and regulate the passage of mature cells from bone marrow to bloodstream. Idiopathic myelofibrosis is an example of the relevance of microenvironment in hematopoiesis. This disease is characterized by fibroblast and basement membrane accumulation, appearance of myofibroblasts and modification of the capillary network and provokes a bone marrow aplasia. In this article we review recent studies on the role of hemopoietic cytokines on stromal cells, in particular on endothelial cells, and propose a double role for CSFs in hematopoiesis to induce the commitment of progenitor cells and to maintain the behavior of bone marrow endothelial cells.