Abstract
Src homology 2 domain-containing protein tyrosine phosphatase substrate 1 (SHPS-1) is a member of the signal regulatory protein family in which the extracellular region interacts with its ligand, CD47. Recent studies have demonstrated that SHPS-1 plays an important role in cell migration and cell adhesion. We demonstrate in this study, using immunohistochemical and flow cytometric analyses, that murine Langerhans cells (LCs) express SHPS-1. Treatment of mice ears with 2,4-dinitro-1-fluorobenzene significantly reduced the number of epidermal LCs, and that reduction could be reversed by pretreatment with mAb to SHPS-1 or the CD47-Fc fusion protein. Treatment with the SHPS-1 mAb in vivo reduced the number of FITC-bearing cells in the lesional lymph nodes after the application of FITC to the skin. The SHPS-1 mAb inhibited the in vivo TNF-alpha-induced migration of LCs. The emigration of dendritic cells expressing I-A(b+) from skin explants to the medium was also reduced by the SHPS-1 mAb. We further demonstrate that the chemotaxis of a murine dendritic cell line, XS52, by macrophage inflammatory protein-3beta was significantly inhibited by treatment with the SHPS-1 mAb or CD47-Fc recombinant protein. Finally, we show that migration of LCs was attenuated in mutant mice that lack the intracellular domain of SHPS-1. These observations show that the ligation of SHPS-1 with the SHPS-1 mAb or with CD47-Fc abrogates the migration of LCs in vivo and in vitro, which suggests that the SHPS-1-CD47 interaction may negatively regulate LC migration.
MeSH terms
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Administration, Topical
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Animals
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Antibodies, Monoclonal / administration & dosage
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Antigens, CD / administration & dosage
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Antigens, CD / genetics
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Antigens, Differentiation / biosynthesis
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Antigens, Differentiation / genetics
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Antigens, Differentiation / immunology
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Antigens, Differentiation / physiology*
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CD11c Antigen / biosynthesis
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CD47 Antigen
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Carrier Proteins / administration & dosage
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Carrier Proteins / genetics
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Cell Count
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Cell Line
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Cell Migration Inhibition
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Cell Movement / immunology*
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Culture Media
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Dinitrofluorobenzene / administration & dosage
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Epidermal Cells*
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Epidermis / immunology
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Epidermis / metabolism*
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Female
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Growth Inhibitors / administration & dosage
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Haptens / administration & dosage
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Haptens / biosynthesis
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Histocompatibility Antigens Class II / biosynthesis
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Immunoglobulin Fc Fragments / genetics
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Injections, Intradermal
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Interleukin-4 / pharmacology
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Langerhans Cells / cytology*
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Langerhans Cells / immunology
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Langerhans Cells / metabolism*
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Lymph Nodes / immunology*
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Lymph Nodes / metabolism*
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Lymph Nodes / pathology
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / immunology
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Membrane Glycoproteins / physiology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Neural Cell Adhesion Molecule L1 / biosynthesis
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Neural Cell Adhesion Molecule L1 / genetics
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Neural Cell Adhesion Molecule L1 / immunology
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Neural Cell Adhesion Molecule L1 / physiology*
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Organ Culture Techniques
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Receptors, Immunologic / biosynthesis
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Receptors, Immunologic / genetics
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Receptors, Immunologic / immunology
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Receptors, Immunologic / physiology*
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Recombinant Fusion Proteins / administration & dosage
Substances
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Antibodies, Monoclonal
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Antigens, CD
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Antigens, Differentiation
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CD11c Antigen
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CD47 Antigen
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Carrier Proteins
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Cd47 protein, mouse
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Culture Media
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Growth Inhibitors
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Haptens
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Histocompatibility Antigens Class II
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I-A(b) antigen, mouse
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Immunoglobulin Fc Fragments
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Membrane Glycoproteins
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Neural Cell Adhesion Molecule L1
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Ptpns1 protein, mouse
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Receptors, Immunologic
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Recombinant Fusion Proteins
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Interleukin-4
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Dinitrofluorobenzene