title: CD63 tetraspanin slows down cell migration and translocates to the endosomal-lysosomal-MIICs route after extracellular stimuli in human immature dendritic cells.
abstract: We analyzed herein whether members of the tetraspanin superfamily are involved in human immature dendritic cell (DC) functions such as foreign antigen internalization, phagocytosis, and cell migration. We show that CD63, CD9, CD81, CD82, and CD151 are present in immature DCs. Whereas CD9 and CD81 are mostly expressed at the cell surface, CD63 and CD82 are also located in intracellular organelles. Complexes of monoclonal antibody (Mab) FC-5.01-CD63 or Fab-5.01-CD63 were rapidly translocated "outside-in" and followed the endocytic pathway through early endosomes and lysosomes, reaching major histocompatibility complex (MHC) class II-enriched compartments (MIICs) in less than one hour. Internalization of CD63 was also observed during Saccharomyces cerevisiae phagocytosis. Moreover, an association of CD63 with the beta-glycan receptor dectin-1 was observed. Mabs against CD9, CD63, CD81, and CD82 enhanced by 50% the migration induced by the chemokines macrophage inflammatory protein-5 (MIP-5) and MIP-1alpha. Concomitantly, Mabs against CD63 and CD82 diminished the surface expression of CD29, CD11b, CD18, and alpha5 integrins. By immunoprecipitation experiments we found that CD63 associated with integrins CD11b and CD18. These results suggest that CD9, CD63, CD81, and CD82 could play a role in modulating the interactions between immature DCs and their environment, slowing their migratory ability. However, only CD63 would intervene in the internalization of complex antigens.
authors.affiliation: Fundación Instituto Leloir, Av Patricias Argentinas 435, 1405 Capital Federal, Argentina.
authors.forename: Adriana R
authors.initials: AR
authors.lastname: Mantegazza
authors.forename: María Marcela
authors.initials: MM
authors.lastname: Barrio
authors.forename: Sandrine
authors.initials: S
authors.lastname: Moutel
authors.forename: Laura
authors.initials: L
authors.lastname: Bover
authors.forename: Markus
authors.initials: M
authors.lastname: Weck
authors.forename: Peter
authors.initials: P
authors.lastname: Brossart
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Teillaud
authors.forename: José
authors.initials: J
authors.lastname: Mordoh
mesh_terms: D015703:Antigens, CD / Q000032:analysis / Q000378:metabolism* / Q000502:physiology*; D002465:Cell Movement; D003713:Dendritic Cells / Q000378:metabolism* / Q000502:physiology; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D051861:Kangai-1 Protein; D008247:Lysosomes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000502:physiology; D010587:Phagocytosis; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism* / Q000502:physiology*; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000502:physiology; D060225:Tetraspanin 28; D060245:Tetraspanin 29; D060149:Tetraspanin 30
chemical_list: D015703:Antigens, CD; C554586:CD63 protein, human; C554798:CD81 protein, human; C497688:CD82 protein, human; C554869:CD9 protein, human; D015395:Histocompatibility Antigens Class I; D051861:Kangai-1 Protein; D008562:Membrane Glycoproteins; D010980:Platelet Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D060225:Tetraspanin 28; D060245:Tetraspanin 29; D060149:Tetraspanin 30