VLA-4 AND VCAM-1 ARE THE PRINCIPAL ADHESION MOLECULES INVOLVED IN THEINTERACTION BETWEEN BLAST COLONY-FORMING CELLS AND BONE-MARROW STROMAL CELLS

The molecular basis and functional significance of interactions betwee n haemopoietic progenitor cells and the stromal microenvironment is st ill poorly understood. Here we investigated a broad panel of surface a dhesion molecules for their involvement. For this purpose, the colony- forming capacity of stroma-adherent BI-CFC, BFU-B and GM-CFC was studi ed. Both mononuclear bone marrow cells (BMC) and bone marrow-derived s tromal cells (BMSC) express a wide variety of adhesion molecules. Howe ver, only antibodies against beta 1-, alpha 4-integrin (both chains of the very late activation antigen-4 (VLA-4)) and vascular cell adhesio n molecule (VCAM-1) inhibited colony formation from stroma-adherent BI -CFC by 50% or more. Antibodies against a panel of other adhesion mole cules, including the alpha 5-integrin chain, were without effect. Subs equent pretreatment experiments revealed that VLA-4 on progenitors int eracted with stromal VCAM-1. The inhibitory antibodies did not interfe re with the clonogenic capacity of but with adhesion of BFU-E and GM-C FC. Whether the inhibitory antibodies act similarly on progenitors whi ch depend on BMSC for growth and/or differentiation, such as BI-CFC, r emains to be determined.