Inhibition of leukocyte-endothelial cell interactions and inflammation by peptides from a bacterial adhesin which mimic coagulation factor X.
Factor X (factor ten) of the coagulation cascade binds to the integrin CD11b/CD18 during inflammation, initiating procoagulant activity on the surface of leukocytes (Altieri, D.C., O.R. Etingin, D.S. Fair, T.K. Brunk, J.E. Geltosky, D.P. Hajjar, and T. S. Edgington. 1991. Science [Wash.DC]. 254:1200-1202). Filamentous hemagglutinin (FHA), an adhesin of Bordetella pertussis also binds to the CD11b/CD18 integrin (Relman D., E. Tuomanen, S. Falkow, D.T. Golenbock, K. Saukkonen, and S.D. Wright. 1990. Cell. 61:1375-1382). FHA and the CD11b/CD18 binding loops of Factor X share amino acid sequence similarity. FHA peptides similar to Factor X binding loops inhibited 125I-Factor X binding to human neutrophils and prolonged clotting time. In addition, ETKEVDG and its Factor X analogue prevented transendothelial migration of leukocytes in vitro and reduced leukocytosis and blood brain barrier disruption in vivo. Interference with leukocyte migration by a coagulation-based peptide suggests a novel strategy for antiinflammatory therapy.
Rozdzinski
E
E
Laboratory of Molecular Infectious Diseases, Rockefeller University, New York 10021.
Sandros
J
J
van der Flier
M
M
Young
A
A
Spellerberg
B
B
Bhattacharyya
C
C
Straub
J
J
Musso
G
G
Putney
S
S
Starzyk
R
R
D018829:Adhesins, Bacterial; D000595:Amino Acid Sequence; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects; D001886:Bordetella pertussis; D018821:CD18 Antigens / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects*; D005170:Factor X / Q000494:pharmacology*; D015951:Factor Xa / Q000187:drug effects; D006388:Hemagglutinins / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007962:Leukocytes / Q000187:drug effects*; D016177:Macrophage-1 Antigen / Q000502:physiology; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D017386:Sequence Homology, Amino Acid; D010566:Virulence Factors, Bordetella
D018829:Adhesins, Bacterial; D000893:Anti-Inflammatory Agents; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D006388:Hemagglutinins; D016177:Macrophage-1 Antigen; D010446:Peptide Fragments; D010566:Virulence Factors, Bordetella; C065273:filamentous hemagglutinin adhesin, Bordetella pertussis; D005170:Factor X; D015951:Factor Xa