title: Interaction between Src homology 2 domain bearing protein tyrosine phosphatase substrate-1 and CD47 mediates the adhesion of human B lymphocytes to nonactivated endothelial cells.
abstract: CD47 modulates a variety of cell functions such as adhesion, spreading, and migration. Using a fusion protein consisting of the extracellular region of Src homology 2 domain bearing protein tyrosine phosphatase substrate-1 (SHPS-1) and the Fc portion of human Ig (SHPS-1-Ig) we investigated the effects of SHPS-1 as a ligand for CD47 on B lymphocytes. Although SHPS-1-Ig binding to human B cell lines was solely mediated via CD47, their binding capacity for soluble and immobilized SHPS-1-Ig varied among cell lines irrespective of the similar expression levels of CD47, suggesting that distinctive affinity/avidity states exist during B cell maturation. Nalm6 cell line and tonsilar B lymphocytes adhered to immobilized SHPS-1-Ig and showed polarization-like morphology. These effects of SHPS-1-Ig were blocked by anti-CD47 mAbs (B6H12 and SE5A5). Wortmannin, a phosphatidylinositol-3 kinase inhibitor, but not pertussis toxin significantly inhibited the polarization induced by the immobilized SHPS-1-Ig. Thus, SHPS-1 acts as an adhesive substrate via CD47 in human B lymphocyte. Immunohistochemical analyses indicated that SHPS-1 is expressed on high endothelial venule as well as macrophages in human tonsils. HUVECs also express SHPS-1 in the absence of any stimuli, and the adhesion of tonsilar B lymphocytes to nonactivated HUVECs was significantly inhibited by SE5A5, indicating that SHPS-1/CD47 interaction is involved in the adhesion. Our findings suggest that SHPS-1/CD47 interaction may contribute to the recruitment of B lymphocytes via endothelial cells under steady state conditions.
authors.affiliation: Department of Internal Medicine and Molecular Science, Graduate School of Medicine B5, Osaka University, Osaka, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tomiyama
authors.forename: Kenji
authors.initials: K
authors.lastname: Oritani
authors.forename: Yoko
authors.initials: Y
authors.lastname: Murayama
authors.forename: Jun
authors.initials: J
authors.lastname: Ishikawa
authors.forename: Hisashi
authors.initials: H
authors.lastname: Kato
authors.forename: Jun-ichiro
authors.initials: J
authors.lastname: Miyagawa Ji
authors.forename: Nakayuki
authors.initials: N
authors.lastname: Honma
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nishiura
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuzawa
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D002460:Cell Line / Q000378:metabolism / Q000502:physiology; D016764:Cell Polarity / Q000235:genetics / Q000276:immunology; D048429:Cell Size / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000494:pharmacology; D007150:Immunohistochemistry; D008208:Lymphatic System / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D014066:Palatine Tonsil / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D011485:Protein Binding / Q000276:immunology; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000502:physiology; D018909:src Homology Domains / Q000235:genetics / Q000276:immunology / Q000502:physiology*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051928:CD47 Antigen; D002352:Carrier Proteins; D007141:Immunoglobulin Fc Fragments; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D011993:Recombinant Fusion Proteins; C497894:CD47 protein, human; C516864:Ptprn protein, rat