EXPRESSION AND FUNCTION OF INTEGRINS ON HEMATOPOIETIC PROGENITOR CELLS

The growth and differentiation of hematopoietic stem cells are highly dependent on regulatory molecules produced by stromal cells of the mar row environment. Evidence has accumulated over the past years which sh ows that adhesive receptors on hematopoietic cells and their ligands o n stromal cells and extracellular matrix play a crucial role in these interactions. Integrins of the beta 1 family, mostly VLA-4 and VLA-5, are the best characterized and have been identified on committed proge nitor cells of the hematopoietic hierarchy as well as on more primitiv e stem cells defined by their long-term repopulating capacity assayed in vitro as well as in vivo. Functional assays demonstrate that most p rogenitor cells efficiently bind to ECM components through beta 1 inte grins and lineage- and maturation stage-specific differences have been described. Evidence exists on the direct control of late erythroid di fferentiation by VLA-LF, but whether or not the triggering of beta 1 i ntegrins is critically required for hematopoietic stem cell functionin g at more immature steps is unclear. Many other integrin and non-integ rin receptors involved in adhesive interactions are expressed on hemat opoietic progenitor cells and tightly regulated during differentiation but their function is still controversial. Our main purpose in this r eview is to describe recent advances in the knowledge of integrin expr ession on hematopoietic progrenitor cells in both mouse and man. The e merging importance of the synergy between integrins and cytokine signa lling pathways in the regulation of hematopoietic differentiation will also be discussed.