Ligation of CD44 with low-molecular-weight hyaluronan and a monoclonal antibody leads to inhibition of drug-induced apoptosis in a human myeloid cell line

Abstract

Adhesive interactions between hematopoietic progenitor cells and extracellular matrix can improve progenitor cell survival. These mechanisms involve a number of different molecules. CD44 is one such molecule, although its molecular basis has not been elucidated. In this study, we investigated the effect of CD44 monoclonal antibodies and hyaluronan, which is a ligand of CD44, on drug-induced apoptosis in human myeloid cell line KG1. Preincubation with anti-CD44 monoclonal antibody J173 or a lower-molecular-weight form of hyaluronan (LMW-HA) could reduce drug-induced apoptosis in a dose-dependent manner from 23·0 ± 1·4% to 5·9 ± 5·0% (p<0·01) or 9·7 ± 1·8% (p<0·01) respectively. On the other hand, another anti-CD44 monoclonal antibody L178 and the native high-molecular-weight polymer of hyaluronan had no effect on drug-induced apoptosis. Furthermore, J173 and LMW-HA induced a rapid increase in tyrosine phosphorylation of intracellular proteins. Genistein, a protein tyrosine kinase inhibitor, abrogated the inhibition of drug-induced apoptosis promoted by J173 and LMW-HA. These results suggest that the anti-apoptotic effect by ligation of CD44 was mediated by tyrosine phosphorylation of intracellular proteins. These data indicate that tyrosine phosphorylation via CD44 is involved in the survival of primitive myeloid cells.