VLA‐4 and VCAM‐1 are the principal adhesion molecules involved in the interaction between blast colony‐forming cells and bone marrow stromal cells

Abstract

The molecular basis and functional significance of interactions between haemopoietic progenitor cells and the stromal microenvironment is still poorly understood. Here we investigated a broad panel of surface adhesion molecules for their involvement. For this purpose, the colony-forming capacity of stroma-adherent Bl-CEC, BFU-E and GM-CFC was studied. Both mononuclear bone marrow cells (BMC) and bone marrow-derived stromal cells (BMSC) express a wide variety of adhesion molecules. However, only antibodies against beta 1-, alpha 4-integrin (both chains of the very late activation antigen-4 (VLA-4)) and vascular cell adhesion molecule (VCAM-1) inhibited colony formation from stroma-adherent Bl-CFC by 50% or more. Antibodies against a panel of other adhesion molecules, including the alpha 5-integrin chain, were without effect. Subsequent pretreatment experiments revealed that VLA-4 on progenitors interacted with stromal VCAM-1. The inhibitory antibodies did not interfere with the clonogenic capacity of but with adhesion of BFU-E and GM-CFC. Whether the inhibitory antibodies act similarly on progenitors which depend on BMSC for growth and/or differentiation, such as BI-CFC, remains to be determined.

Downregulation of Integrin Receptor-Signaling Genes by Epstein-Barr Virus EBNA 3C via Promoter-Proximal and -Distal Binding Elements

“…The ␣4 integrin and ␤1 integrin subunits encoded by the ITGA4 and ITGB1 genes heterodimerize to form the major integrin receptor (␣4␤1) expressed in B-lymphoid cells. ␣4␤1 integrin mediates migration through association with ligands, including fibronectin and vascular cell adhesion molecule-1 (VCAM-1) (2,11,17,35). Interestingly, ADAM28 is highly expressed in B lymphocytes and also functions as a ligand for ␣4␤1 integrin, with binding of soluble ADAM28 enhancing ␣4␤1 integrin adhesion to VCAM-1 (7,31).…”

Human macrophages rescue myoblasts and myotubes from apoptosis through a set of adhesion molecular systems

“…Among the 375 genes represented on the DNA macroarray membrane we used, 12 (Table 1) had products known to be involved in anti-apoptotic signals mediated by cell-cell contacts. Four of these products were constitutively expressed by human mpcs and had their counterligands expressed by human MPs (Table 1), as follows: (1) VCAM-1 binding to VLA-4 (␣4␤1 integrin); this adhesion system mediates the protective effects of MPs to erythroblasts (Hanspal and Hanspal, 1994;Sadahira and Mori, 1999), of stromal cells to haematopoietic stem cells, B cells and plasma cells (Koopman et al, 1994;Oostendorp et al, 1995;Wang et al, 1998;Hayashida et al, 2000;Minges Wols et al, 2002;Hall et al, 2004) and of endothelial cells to mast cells (Mierke et al, 2000). It is also involved in protection of T cells and retinal ganglion cells (Rose et al, 2000;Leussink et al, 2002;Leu et al, 2004).…”

Kinetics of in vivo homing and recruitment into cycle of hematopoietic cells are organ-specific but CD44-independent

“…Stromal cells also express a variety of adhesion molecules on their surfaces which allow them to interact directly with hematopoietic cells. 2 In vitro studies suggest that the strength of the interactions of hematopoietic cells with extracellular matrix proteins depends on transient activation signals stimulated by concomitant interactions of the hematopoietic cells with cytokines like GM-CSF and Steel factor (SF) 3 or certain costimulatory adhesion molecules like the ␤1-integrins, CD44 and ICAM-3. [4][5][6] Such activation signals peak between 15 min and 2 h after ligand binding and then decline, thereby providing a dynamic process of adhesion and detachment which facilitates the ability of hematopoietic cells to move through the type of stromal cell network that extends throughout the bone marrow cavity.…”