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 t he 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. S cience [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, an d S. D. Wright. 1990. Cell. 61:1375-1382). FHA and the CD11b/CD18 bind ing loops of Factor X share amino acid sequence similarity. FHA peptid es similar to Factor X binding loops inhibited I-125-Factor X binding to human neutrophils and prolonged clotting time. In addition, ETKEVDG and its Factor X analogue prevented transendothelial migration of leu kocytes in vitro and reduced leukocytosis and blood brain barrier disr uption in vivo. Interference with leukocyte migration by a coagulation -based peptide suggests a novel strategy for antiinflammatory therapy.