ADHESION OF HUMAN HEMATOPOIETIC PROGENITOR CELLS TO BONE-MARROW-DERIVED STROMAL CELLS IS ENHANCED BY ANTIBODIES TO CD44

It has been suggested that CD44 mediates adhesive interactions between hematopoietic progenitor cells and the stromal microenvironment. Liga nds of CD44 include several extracellular matrix components, such as h yaluronic acid and fibronectin. Antibodies against CD44 have been show n to induce homotypic T cell aggregation, and to stimulate T and natur al killer cell activity. We hypothesized that CD44 could similarly amp lify interactions between blast-colony-forming cells and bone marrow s tromal cells (BMSCs). Indeed, we have previously found that the anti-C D44 antibody NKI-P2 enhanced VLA-4-dependent interactions. Here, we st udied an additional panel of nineteen anti-CD44 antibodies from the 5t h Workshop on Leukocyte Differentiation antigens, to find out whether amplification was associated with a particular CD44 epitope. None of t hese antibodies showed inhibitory activity, whereas nine significantly increased the number of blast colonies more than 2-fold. Seven of the se recognized epitope 1, and two epitope 2. More than 4-fold enhanceme nt was only observed with epitope 1 antibodies: 4.C3 (4.4-fold), 212.3 (6.3-fold), L178 (9.1-fold), and NIH44-1 (9.2-fold). Our data suggest that primarily epitope 1 is associated with enhancement of colony for mation. Furthermore, the findings support a role for CD44 as an amplif ier in progenitor-BMSC interactions.