title: Novel CD47-dependent intercellular adhesion modulates cell migration.
abstract: CD47 is a ubiquitously expressed plasma membrane protein, also known as Integrin Associated Protein, that modulates cell adhesion both through alteration of the avidity of integrin binding and through interaction with its own ligands, the extracellular matrix protein thrombospondin (TSP) and the plasma membrane response regulator SIRPalpha1. We now show that CD47 expression on fibroblasts can induce intercellular adhesion resulting in cell aggregation in the absence of active integrins, SIRPalpha1 binding, and detectable TSP. CD47-expressing cells preferentially bind to other CD47-expressing cells, and intercellular adhesion requires stimulation by serum or a CD47-binding peptide from TSP. Cell-cell adhesion is inhibited by pertussis toxin and C. difficile toxin B, and both adherent and aggregating CD47-expressing fibroblasts have more rac in the GTP bound state than CD47-deficient cells. Spontaneous migration of Jurkat lymphocytes through a fibroblast monolayer is decreased by fibroblast expression of CD47, consistent with an increased barrier function of the CD47 expressing cells. The lymphocyte chemoattractant SDF-1alpha stimulates migration of Jurkat cells through this monolayer only if both the lymphocytes and fibroblasts express CD47, and the inhibition of migration by a CD47-interacting peptide from TSP similarly requires CD47 expression on both cell types. Thus, signaling dependent on both heterotrimeric and rho family GTPases can induce CD47 to participate in cell-cell interactions independent of known ligands that enhance intercellular adhesion and modulate cell migration.
authors.affiliation: Program in Microbial Pathogenesis and Host Defense, University of California, San Francisco, California, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rebres
authors.forename: Kimberly
authors.initials: K
authors.lastname: Kajihara
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Brown
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology; D001427:Bacterial Toxins / Q000494:pharmacology; D051928:CD47 Antigen / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000276:immunology; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D008214:Lymphocytes / Q000378:metabolism / Q000502:physiology; D051379:Mice; D037342:Pertussis Toxin / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D019699:Thrombospondins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D051928:CD47 Antigen; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D011994:Recombinant Proteins; D019699:Thrombospondins; C031815:toxB protein, Clostridium difficile; D037342:Pertussis Toxin; D020962:Heterotrimeric GTP-Binding Proteins; D020744:rac GTP-Binding Proteins