Prokaryotic peptides that block leukocyte adherence to selectins.
Pertussis toxin binds target cells through the carbohydrate recognition properties of two subunits, S2 and S3, which share amino acid sequence similarity with the lectin domains of the eukaryotic selectin family. Selectins appear on inflamed endothelial cells and promote rolling of leukocytes by reversibly binding carbohydrates. S2, S3, and synthetic peptides representing their carbohydrate recognition domains competitively inhibited adherence of neutrophils to selectin-coated surfaces and to endothelial cells in vitro. These proteins and peptides also rapidly upregulated the function of the leukocyte integrin CD11b/CD18. These findings implicate mimicry of eukaryotic selectins by prokaryotic adhesive ligands and link the mechanisms underlying leukocyte trafficking to microbial pathogenesis.
Rozdzinski
E
E
Laboratory of Molecular Infectious Diseases, Rockefeller University, New York, New York 10021.
Burnette
W N
WN
Jones
T
T
Mar
V
V
Tuomanen
E
E
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism; D001667:Binding, Competitive; D018821:CD18 Antigens; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism*; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000166:cytology; D019041:L-Selectin; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008969:Molecular Sequence Data; D019007:P-Selectin; D037342:Pertussis Toxin; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D010566:Virulence Factors, Bordetella / Q000737:chemistry* / Q000378:metabolism
D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016177:Macrophage-1 Antigen; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D010566:Virulence Factors, Bordetella; D019041:L-Selectin; D037342:Pertussis Toxin