Expression and Function of Integrins on Hematopoietic Progenitor Cells

Abstract

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 β1 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 β1 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 β1 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 progrenitor 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.

Maturation and enucleation of primitive erythroblasts during mouse embryogenesis is accompanied by changes in cell-surface antigen expression

“…We next asked whether EryP, like definitive erythroblasts, 56,57 show regulated expression of adhesion molecules during their maturation. No expression of ␣4, ␣5, and ␣6 integrins was detected on EryP/GFP ϩ cells at E9.5-10.5 (Table 3; data not shown).…”

In Vivo Roles of Integrins During Leukocyte Development and Traffic: Insights from the Analysis of Mice Chimeric for α5, αv, and α4 Integrins

“…␣ 5 , ␣ V , and ␣ 4 integrins recognize different sites on fibronectin, and they also bind other specific ligands, including vitronectin for ␣ V integrins and VCAM-1 and mucosal addressin cell adhesion molecule-1 (MAd-CAM-1) 6 for ␣ 4 integrins (2,3). Expression studies have shown the presence of integrins on leukocyte progenitors and their differential regulation among lineages (1,4). In particular, ␣ 4 and ␣ 5 integrins are expressed early during hemopoietic development, but they are down-regulated during neutrophil development.…”

Rapidly mobilizable stem cells. Do they belong to a special subpopulation?

“…Although the mechanism by which stem cells are released from the bone marrow is not completely understood, data published during the last few years proved the expression of a wide range of adhesion molecules (e.g., very late-acting antigen-4 [VLA-41, VLA-5, leukocyte function-associated antigen-] [LFA-I], LFA-3, L-selectin) on CD34' progenitors, suggesting their role in anchorage of stem cells in the bone marrow [24].…”