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 marrow environment. Evidence has accumulated over the past years which shows that adhesive receptors on hematopoietic cells and their ligands on 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 progenitor cells of the hematopoietic hierarchy as well as on more primitive stem cells defined by their long-term repopulating capacity assayed in vitro as well as in vivo. Functional assays demonstrate that most progenitor cells efficiently bind to ECM components through beta 1 integrins and lineage- and maturation stage-specific differences have been described. Evidence exists on the direct control of late erythroid differentiation by VLA-4, but whether or not the triggering of beta 1 integrins is critically required for hematopoietic stem cell functioning at more immature steps is unclear. Many other integrin and non-integrin receptors involved in adhesive interactions are expressed on hematopoietic progenitor cells and tightly regulated during differentiation but their function is still controversial. Our main purpose in this review is to describe recent advances in the knowledge of integrin expression on hematopoietic progenitor cells in both mouse and man. The emerging importance of the synergy between integrins and cytokine signalling pathways in the regulation of hematopoietic differentiation will also be discussed.
Coulombel
L
L
INSERM U 362, Institut Gustave-Roussy, Villejuif, France.
Auffray
I
I
Gaugler
M H
MH
Rosemblatt
M
M
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells; D002448:Cell Adhesion; D002454:Cell Differentiation; D002455:Cell Division; D003238:Connective Tissue / Q000378:metabolism; D003239:Connective Tissue Cells; D016207:Cytokines / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D039041:Integrin alpha4beta1; D019012:Integrin beta1 / Q000235:genetics / Q000502:physiology; D016023:Integrins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D017469:Receptors, Fibronectin / Q000502:physiology; D016201:Receptors, Lymphocyte Homing / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D016207:Cytokines; D016326:Extracellular Matrix Proteins; D039041:Integrin alpha4beta1; D019012:Integrin beta1; D016023:Integrins; D017469:Receptors, Fibronectin; D016201:Receptors, Lymphocyte Homing