Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adhesins, Bacterial*
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Amino Acid Sequence
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Anti-Inflammatory Agents / pharmacology
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Blood Coagulation / drug effects
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Blood-Brain Barrier / drug effects
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Bordetella pertussis
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CD18 Antigens / physiology
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Cell Adhesion / drug effects
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Cell Adhesion Molecules / pharmacology
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Cell Communication / drug effects
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Chemotaxis, Leukocyte / drug effects
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Endothelium, Vascular / drug effects*
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Factor X / pharmacology*
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Factor Xa / drug effects
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Hemagglutinins / pharmacology*
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Humans
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Inflammation / metabolism*
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Leukocytes / drug effects*
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Macrophage-1 Antigen / physiology
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Molecular Mimicry
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Molecular Sequence Data
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Monocytes / drug effects
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Peptide Fragments / pharmacology*
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Protein Binding / drug effects
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Sequence Homology, Amino Acid
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Virulence Factors, Bordetella*
Substances
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Adhesins, Bacterial
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Anti-Inflammatory Agents
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CD18 Antigens
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Cell Adhesion Molecules
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Hemagglutinins
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Macrophage-1 Antigen
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Peptide Fragments
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Virulence Factors, Bordetella
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filamentous hemagglutinin adhesin, Bordetella pertussis
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Factor X
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Factor Xa