CD44 OCCUPANCY PREVENTS MACROPHAGE MULTINUCLEATION

Cells of the mononuclear phagocyte lineage have the capability to adhe re to and fuse with each other and to differentiate into osteoclasts a nd giant cells. To investigate the macrophage adhesion/fusion mechanis m, we focused our attention on CD44, a surface glycoprotein known to p lay a role in hematopoietic cell-cell adhesion. We report that CD44 ex pression by macrophages is highly and transiently induced by fusogenic conditions both in vitro and in vivo. We show that CD44 ligands, hyal uronic acid, chondroitin sulfates, and osteopontin prevent macrophage multinucleation. In addition, we report that the recombinant extracell ular domain of CD44 binds fusing macrophages and prevents multinucleat ion in vitro. These data suggest that CD44 may control the mononucleat ed status of macrophages in tissues by virtue of mediating cell-cell i nteraction.