AN INVESTIGATION INTO THE ROLE OF INTEGRINS DURING ERYTHROPOIESIS: WHAT INTERACTIONS ARE INVOLVED, HOW ARE THEY REGULATED, AND HOW DO THEY AFFECT ERYTHROID DIFFERENTIATION

Abstract

In human, erythropoiesis occurs in cellular structures within the bone marrow called erythroblastic islands. These islands comprise a central macrophage encircled by differentiating erythroblasts. Within the island there are multiple cellular interactions mediated by the integrin family of adhesion molecules. Integrins are a well characterised group of adhesion molecules comprising of an alpha and a beta subunit. Distinct combinations of alpha and beta subunits result in an enormous range of integrins with different binding partners, but which are all involved in signalling events that produce cellular effects. Four integrins, α4β1, α5β1, αIIbβ3, and αLβ2, are expressed on human erythroblasts during erythropoiesis. In this review I aim to investigate the expression, role and ligand of these integrins during erythropoiesis. The results show the importance of α4β1 during terminal differentiation while the importance of α5β1 is with proliferation/differentiation under stress conditions. α4β1is expressed throughout maturation and its significant ligand is VCAM-1 on the macrophage while α5β1 expression is limited to early erythroid differentiation and it binds only fibronectin. αIIbβ3 has the most restricted integrin expression in erythroid cells and little is known about its function. αLβ2 adhesion to ICAM-2, -3 and -4 may be important for adhesion between proerythroblasts and other erythroid cells in the island. In conclusion, although essential for erythropoiesis, these four integrins have predominantly been studied individually and in mice so their expression, roles and ligands in humans are not fully comprehended. Further investigation is required to fully comprehend the function of these integrins play in human erythropoiesis.