2 DIFFERENT FUNCTIONS FOR CD44 PROTEINS IN HUMAN MYELOPOIESIS

CD44 is important during myelopoiesis, although the contributions of v ariant CD44 proteins are unclear. We show here that in human long-term bone marrow culture antibodies recognizing a CD44 NH2-terminal epitop e (mab 25-32) or a CD44v6 epitope (mab VFF18) inhibit myelopoiesis, Ho wever, mab 25-32 but not mab VFF18 affects myeloid colony formation. T hese data suggest that an early precursor cell compartment is the targ et for the 25-32 antibody, whereas the mab VFF18 targets later stages in myelopoiesis, Since the bulk of hemopoietic precursor cells are neg ative for the v6 epitope and only a minor subset of myeloid cells expr ess the v6 epitope, we have used several human myeloid progenitor cell lines to unravel the function of different CD44 proteins, These cell lines produce variant CD44 proteins, predominantly a new variant CD44v 4-v10, when stimulated towards myeloid differentiation. Features that can be acquired by the expression of CD44v4-v10 are an increased hyalu ronate (HA) and a de novo chondroitin sulphate A (CS-A) binding. Altho ugh, the expression of CD44v4-v10 per se is necessary for HA and CS-A binding, the protein backbone seems to require appropriate glycosylati on. HA binding results in CD44-mediated cellular self-aggregation and adhesion to the stromal cell line MS-5. In summary, our data suggest t hat different CD44 proteins are important for at least two different s teps in myelopoiesis.