title: Inhibition of P-selectin-mediated cell adhesion by a sulfated derivative of sialic acid.
abstract: P-selectin, a carbohydrate-binding cell adhesion molecule expressed on activated endothelial cells and platelets, plays a key role in the recruitment of leukocytes to inflammatory and hemorrhagic sites. It simultaneously recognizes a sialic acid-containing carbohydrate chain and the sulfated tyrosine residues of a specific counter-receptor expressed on the leukocyte surface. We examined the inhibitory effects of a synthetic sulfated derivative of sialic acid (NMSO3) on P-selectin-mediated cell adhesion and found the following: (1) P-selectin/IgG chimera bound to immobilized NMSO3. (2) The binding of P-selectin/IgG chimera to purified P-selectin glycoprotein ligand-1 was inhibited by soluble NMSO3. (3) The adhesion of HL60 cells to P-selectin-expressing CHO cells was inhibited by NMSO3. (4) NMSO3 inhibited P-selectin-induced tumor necrosis factor-alpha production in monocytes and activated platelet-induced generation of reactive oxygen species in neutrophils. In conclusion, NMSO3 acts as a specific inhibitor for P-selectin-mediated cell adhesion and for adhesion-dependent leukocyte activation.
authors.affiliation: Department of Microbiology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Shodai
authors.forename: Junsuke
authors.initials: J
authors.lastname: Suzuki
authors.forename: Sanae
authors.initials: S
authors.lastname: Kudo
authors.forename: Saotomo
authors.initials: S
authors.lastname: Itoh
authors.forename: Masaki
authors.initials: M
authors.lastname: Terada
authors.forename: Shuji
authors.initials: S
authors.lastname: Fujita
authors.forename: Hajime
authors.initials: H
authors.lastname: Shimazu
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tsuji
mesh_terms: D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006801:Humans; D007963:Leukocytes, Mononuclear; D008055:Lipids / Q000494:pharmacology*; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D018375:Neutrophil Activation / Q000187:drug effects / Q000502:physiology*; D009504:Neutrophils; D019007:P-Selectin / Q000502:physiology*; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C413863:(2,2-bis(docosyloxymethyl)propyl-5-acetamido-3,5-dideoxy-4,7,8,9-tetra-O-(sodium oxysulfonyl)glycero-alpha-galacto-2-nonulopyranosid)onate; D008055:Lipids; D019007:P-Selectin; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D019158:N-Acetylneuraminic Acid