VLA-4 and VCAM-1 are the principal adhesion molecules involved in the interaction between blast colony-forming cells and bone marrow stromal cells.
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.
GSF-Forschungszentrum für Umwelt und Gesundheit, Institut für Experimentelle Hämatologie, München, Germany.
R A
RA
Oostendorp
G
G
Reisbach
E
E
Spitzer
K
K
Thalmeier
H
H
Dienemann
H G
HG
Mergenthaler
P
P
Dörmer
D000911:Antibodies, Monoclonal / Q000502:physiology; D001853:Bone Marrow / Q000502:physiology*; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology*; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*; D017154:Stromal Cells / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology*
D000911:Antibodies, Monoclonal; D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1