Abstract
Sulfatide has been reported to activate leukocytes through L-selectin. Here we provide evidence that sulfatide binds to and activates leukocytes through both L-selectin-dependent and -independent pathways. Rat leukocytes of various sources shed surface L-selectin after phorbol myristate acetate (PMA) treatment, however, these cells retained the ability to bind sulfatide. In addition, sulfatide also bound to an L-selectin-negative cell line EL-4, and the binding was up-regulated by PMA. Sulfatide induced aggregation of L-selectin-positive lymphocytes, which was highly dependent on divalent cations, protein tyrosine kinases (PTK), and protein kinase C (PKC), but was independent of beta1 and beta2 integrins. In contrast, sulfatide-induced EL-4 cell aggregation required an LFA-1/ICAM-1 adhesion pathway but not PTK and PKC. A sulfatide receptor of 65 kDa was isolated from EL-4 cells. Taken together, this study suggests that sulfatide can bind to and activate leukocytes through an L-selectin-independent molecule and triggers signal transduction pathways different from those induced by L-selectin activation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / pharmacology
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Binding Sites
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CD18 Antigens / physiology
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Cations, Divalent / pharmacology
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Cattle
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Cell Adhesion / drug effects*
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Cell Aggregation / drug effects
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Cells, Cultured / drug effects
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Consensus Sequence
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Culture Media / pharmacology
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Culture Media, Serum-Free / pharmacology
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Dogs
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Endothelium, Vascular / cytology
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Enzyme Inhibitors / pharmacology
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Fetal Blood
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Integrin beta1 / physiology
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Intercellular Adhesion Molecule-1 / physiology
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Jugular Veins
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L-Selectin / physiology*
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Leukocytes / drug effects*
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Leukocytes / physiology
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Lymph Nodes / cytology
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Lymphocyte Function-Associated Antigen-1 / physiology
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Lymphoma / pathology
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Male
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Molecular Weight
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Neoplasm Proteins / physiology
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Protein Kinase C / physiology
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Protein-Tyrosine Kinases / physiology
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Rats
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Rats, Wistar
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Receptors, Cell Surface / chemistry
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Receptors, Cell Surface / drug effects
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Receptors, Cell Surface / isolation & purification*
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Receptors, Cell Surface / metabolism
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Signal Transduction / drug effects
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Specific Pathogen-Free Organisms
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Sulfoglycosphingolipids / metabolism*
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Sulfoglycosphingolipids / pharmacology
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T-Lymphocytes / metabolism
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T-Lymphocytes / pathology
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Tetradecanoylphorbol Acetate / pharmacology
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Tumor Cells, Cultured
Substances
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Antibodies, Monoclonal
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CD18 Antigens
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Cations, Divalent
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Culture Media
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Culture Media, Serum-Free
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Enzyme Inhibitors
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Integrin beta1
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Lymphocyte Function-Associated Antigen-1
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Neoplasm Proteins
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Receptors, Cell Surface
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Sulfoglycosphingolipids
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sulfatide receptor
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Intercellular Adhesion Molecule-1
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L-Selectin
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I(3)SO3-galactosylceramide
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Protein-Tyrosine Kinases
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Protein Kinase C
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Tetradecanoylphorbol Acetate