Shedding of the CD44 adhesion molecule from leukocytes induced by anti-CD44 monoclonal antibody simulating the effect of a natural receptor ligand.

The CD44 adhesion molecule, playing an important role in leukocyte extravasation, was down-regulated by PMA and ionomycin on granulocytes and by an immobilized or soluble anti-CD44 mAb both on granulocytes and lymphocytes. Soluble labeled CD44 molecules of lower apparent molecular mass as compared to their membrane counterparts were isolated from culture supernatants of stimulated surface iodinated cells. Shedding rather than internalization is the mechanism found to be responsible for the loss of CD44 from the cell surface. The size of the soluble CD44 shed from the cells stimulated in vitro corresponds to soluble CD44 isolated from human serum. These data suggest that shedding, induced by anti-CD44 antibody simulating the effect of a natural CD44 ligand, is an important regulatory mechanism controlling surface CD44 expression on leukocytes in vivo.