ANTIBODIES TO THE BETA-1-INTEGRIN CHAIN, CD44, OR ICAM-3 STIMULATE ADHESION OF BLAST COLONY-FORMING CELLS AND MAY INHIBIT THEIR GROWTH

Early hematopoietic progenitor cells adhere to bone marrow stromal cel ls (BMSCs) mainly through VLA-4/VCAM-1 interactions. However, many adh esion molecules are expressed by these cell types. Cell adhesion molec ules not only mediate adhesion; some are also capable of triggering ce llular signaling events. These signals can be induced by several anti- adhesion molecule antibodies. In this study, we investigated the effec ts of several of such stimulatory antibodies against alpha L (CD11a), alpha 4 (CD49d), and beta 1 (CD29) integrin chains, ICAM-3 (CD50), CD3 4, CD44, and CD45. All antibodies reacted strongly with CD34-positive bone marrow (BM) cells, but only those against beta 1 integrin (TS2/16 , Lia1/2) or CD44 (NKI-P2) reacted with BMSCs. To test the ability of these antibodies to stimulate adhesive interactions, we analyzed their effect on stroma-adherent blast colony-forming cells (B1-CFCs). We fo und that TS2/16 (anti-beta 1 integrin), NKI-P2 (anti-CD44), and 152-2D 11 (anti-ICAM-3) enhanced adhesion of BM mononuclear cells to stroma ( TS2/16:3.4-fold, NKI-P2: 3.8-fold, 152-2D11: 2.6-fold) when compared w ith isotype-control-treated cells. The increase in stroma-adherent cel ls was accompanied by an increase in Day 5-7 blast colonies of 3.8-, 2 .6-, and 1.9-fold, respectively. One antibody against CD29:Lia1/2 stro ngly inhibited the formation of blast colonies, an effect that was at least partially caused by its growth-inhibitory activity. Of the other antibodies tested, none displayed growth-modulatory activity. We have found previously that B1-CFCs depend strongly on VLA-4 and VCAM-1. Ho wever, in TS2/16- or 152-2D11-treated cultures, we observed not only t hese, but also VLA-5-dependent adhesive interactions. In contrast, VLA -5 did not appear to be involved in NKI-P2-treated cultures. Our data indicate that interactions mediated by beta 1-integrins are involved i n the growth of B1-CFCs. Furthermore, interactions mediated by beta 1- integrins, CD44, and ICAM-3 differentially modulate VLA-4- and VLA-5-d ependent progenitor/BMSC interactions.