ADHESIVE AND OR SIGNALING FUNCTIONS OF CD44 ISOFORMS IN HUMAN DENDRITIC CELLS/

The regulation and function of the CD44 family of surface glycoprotein s were investigated in human monocyte-derived dendritic cells (DCs), V ariant CD44 isoform transcripts encoding exons v3, v6, and v9 are diff erently regulated during the differentiation of monocytes into DCs. TN F-alpha treatment, which induces the maturation of DCs, up-regulates t he expression of all v3-, v6-, and v9-containing isoforms examined, CD 44 molecules are involved in the adhesion of DCs to immobilized hyalur onate (HA), and v3- and v6-containing variants participate in this fun ction, whereas anti-CD44v9 mAbs were unable to inhibit DC adhesion to HA. The consequences of ligand binding to CD44 were examined ibg cultu ring DCs on dishes coated with HA or various anti-CD44 mAbs, HA, the a nti-pan CD44 mAb J173, and mAbs directed against v6- and v9-containing (but not v3-containing) isoforms provoked DC aggregation, phenotypic and functional maturation, and the secretion of IL-8, TNF-alpha, IL-1 beta, and granulocyte-macrophage CSF, In addition, IL-6, IL-10, and IL -12 were released by DCs stimulated with either J173 or HA, although t hese cytokines were not detected or were found only at low levels in t he culture supernatants of DCs treated with anti-CD44v6 or anti-CD44v9 mAbs, Our study points to distinct capacities of the v3-, v6-, and v9 -containing isoforms expressed by human DCs to mediate cell adhesion t o EIA and/or a signal inducing DC maturation and the secretion of cyto kines.