Peptide from a prokaryotic adhesin blocks leukocyte migration in vitro and in vivo.
The integrin CD11b/CD18 promotes leukocyte extravasation during inflammation. Filamentous hemagglutinin (FHA) of Bordetella pertussis binds to CD11b/CD18, raising the possibility that peptides derived from FHA might inhibit leukocyte migration. The Arg-Gly-Asp (RGD) sequence of FHA has been suggested to modulate binding of ligands to CD11b/CD18. Peptides derived from this region inhibited adherence and transendothelial migration of neutrophils in vitro and prevented recruitment of leukocytes into the cerebrospinal fluid in an experimental model of meningitis in rabbits. The mechanism of the antiinflammatory effect may involve modulation of the activity of CD11b/CD18 through peptide interaction with the leukocyte response integrin/integrin-associated protein complex.
Rozdzinski
E
E
Laboratory of Molecular Infectious Diseases, Rockefeller University, New York, New York 10021, USA.
Spellerberg
B
B
van der Flier
M
M
Bhattacharyya
C
C
Hoepelman
A I
AI
Moran
M A
MA
Jarpe
A
A
Putney
S D
SD
Starzyk
R M
RM
Tuomanen
E
E
D018829:Adhesins, Bacterial / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D001886:Bordetella pertussis / Q000276:immunology; D018821:CD18 Antigens / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular; D006388:Hemagglutinins / Q000494:pharmacology*; D006801:Humans; D019041:L-Selectin; D016177:Macrophage-1 Antigen / Q000502:physiology*; D008581:Meningitis / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides; D010446:Peptide Fragments / Q000494:pharmacology*; D011817:Rabbits; D016897:Respiratory Burst; D014471:Umbilical Veins; D010566:Virulence Factors, Bordetella
D018829:Adhesins, Bacterial; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D006388:Hemagglutinins; D016177:Macrophage-1 Antigen; D009842:Oligopeptides; D010446:Peptide Fragments; D010566:Virulence Factors, Bordetella; C065273:filamentous hemagglutinin adhesin, Bordetella pertussis; D019041:L-Selectin; C047981:arginyl-glycyl-aspartic acid