Inhibition of P-selectin-mediated cell adhesion by a sulfated derivative of sialic acid.
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.
Shodai
Tomonori
T
Department of Microbiology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Suzuki
Junsuke
J
Kudo
Sanae
S
Itoh
Saotomo
S
Terada
Masaki
M
Fujita
Shuji
S
Shimazu
Hajime
H
Tsuji
Tsutomu
T
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
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