Sulfatide binding and activation of leukocytes through an L-selectin-independent pathway.
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.
Department of Bioregulation, Biomedical Research Center, Osaka University Medical School, Japan. zding@is.dal.ca
Z
Z
Ding
H
H
Kawashima
M
M
Miyasaka
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001665:Binding Sites; D018821:CD18 Antigens / Q000502:physiology; D002413:Cations, Divalent / Q000494:pharmacology; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects*; D002449:Cell Aggregation / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D016384:Consensus Sequence; D003470:Culture Media / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000166:cytology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005312:Fetal Blood; D019012:Integrin beta1 / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007601:Jugular Veins; D019041:L-Selectin / Q000502:physiology*; D007962:Leukocytes / Q000187:drug effects* / Q000502:physiology; D008198:Lymph Nodes / Q000166:cytology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D008223:Lymphoma / Q000473:pathology; D008297:Male; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000187:drug effects / Q000302:isolation & purification* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013047:Specific Pathogen-Free Organisms; D013433:Sulfoglycosphingolipids / Q000378:metabolism* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D002413:Cations, Divalent; D003470:Culture Media; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D019012:Integrin beta1; D016169:Lymphocyte Function-Associated Antigen-1; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; D013433:Sulfoglycosphingolipids; C412037:sulfatide receptor; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; C084124:I(3)SO3-galactosylceramide; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate