Antiinflammatory effects in experimental meningitis of prokaryotic peptides that mimic selectins.
The lectin domains of two subunits of pertussis toxin, S2 and S3, share amino acid sequence similarity with the lectin domains of the eukaryotic selectin family. During inflammation, selectins appear on endothelial cells and promote recruitment of leukocytes by reversibly binding carbohydrates. Synthetic peptides representing the carbohydrate recognition domains of S2 and S3 competitively inhibited adherence of neutrophils to endothelial cells in vitro. For some peptides, this antiinflammatory effect occurred without up-regulation of the function of the leukocyte integrin CD11b/CD18. Intravenous administration of peptides to animals with meningitis disrupted recruitment of leukocytes into the cerebrospinal fluid. These findings indicate that peptides derived from prokaryotic members of the selectin family have therapeutic antiinflammatory potential.
Rozdzinski
E
E
Laboratory of Molecular Infectious Diseases, Rockefeller University, New York, New York 10021.
Jones
T
T
Burnette
W N
WN
Burroughs
M
M
Tuomanen
E
E
D000595:Amino Acid Sequence; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism; D018821:CD18 Antigens; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000737:chemistry; D002478:Cells, Cultured; D004195:Disease Models, Animal; D019040:E-Selectin; D006801:Humans; D016023:Integrins / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008581:Meningitis / Q000188:drug therapy*; D008969:Molecular Sequence Data; D019007:P-Selectin; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D037342:Pertussis Toxin; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry; D011817:Rabbits; D017386:Sequence Homology, Amino Acid; D015854:Up-Regulation; D010566:Virulence Factors, Bordetella / Q000737:chemistry / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016023:Integrins; D016177:Macrophage-1 Antigen; D019007:P-Selectin; D010446:Peptide Fragments; D010980:Platelet Membrane Glycoproteins; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin