PDF herunterladen
Thromb Haemost 1992; 67(03): 289-291
DOI: 10.1055/s-0038-1648433
Rapid Communications
Schattauer GmbH Stuttgart

Hirudin C-Terminal Fragments lnhibit Thrombin Induced Neutrophil Chemotaxis

Judith K Rowand
1   Department of Chemistry, The Ohio State University, Columbus, Ohio, USA
,
Philip Marucha
2   College of Dentistry, The Ohio State University, Columbus, Ohio, USA
,
Lawrence J Berliner
1   Department of Chemistry, The Ohio State University, Columbus, Ohio, USA
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 11. November 1991

Accepted after revision 12. Dezember 1991

Publikationsdatum:
03. Juli 2018 (online)

Auch verfügbar auf
  als PDF herunterladen  Lizenzen und Reprints

Summary

Since native hirudin blocks the thrombin induced chemotaxis response of neutrophils, we examined whether hirudin C-terminal peptides were also capable of this inhibition. The studies showed that thrombin induced human neutrophil chemotaxis was effectively blocked by the C-terminal hirudin peptide analogs, Gly-Asp-Phe-Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-Gin (12-mer[54-65]) and Thr-Pro-Lys-Pro-Gln-Ser-His-Asn-Asp-Gly-Asp-Phe-Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-Gln (21-mer[45-65]). Furthermore, neither peptide had an effect on formyl-L-methionyl-L-leucyl-L-phenylalanine induced chemotaxis. The results suggest that binding of the hirudin C-terminal peptides block the thrombin chemotactic domain.

 

  • References

  • 1 Henschen A, Lottspeich F, Kehl M, Southan C. Covalent structure of fibrinogen. Ann NY Acad Sci 1983; 408: 28-43
    CrossrefPubMedSuche in Google Scholar
  • 2 Scheraga HA. Interaction of thrombin and fibrinogen and the polymerization of fibrin monomer. Ann NY Acad Sci 1983; 408: 330-343
    CrossrefPubMedSuche in Google Scholar
  • 3 Lorand L, Konishi K. Activation of the fibrin stabilizing factor of plasma by thrombin. Arch Biochem Biophys 1984; 105: 58-67
    PubMedSuche in Google Scholar
  • 4 Davey MG, Luscher EF. Actions of thrombin and other coagulant and proteolytic enzymes on blood platelets. Nature (London) 1967; 216: 857-858
    CrossrefPubMedSuche in Google Scholar
  • 5 Bar-Shavit R, Kahn A, Fenton II JW, Wilner GD. Chemotactic response of monocytes to thrombin. J Cell Biol 1983; 96: 282-285
    CrossrefPubMedSuche in Google Scholar
  • 6 Bar-Shavit R, Kahn A, Fenton II JW, Wilner GD. Receptor-mediated chemotactic response of a macrophage cell line (J774) to thrombin. Lab Invest 1983; 49: 702-707
    PubMedSuche in Google Scholar
  • 7 Bar-Shavit R, Kahn A, Wilner GD, Fenton II JW. Monocyte chemotaxis: Stimulation by specific exosite region in thrombin. Science 1983; 220: 728-731
    CrossrefPubMedSuche in Google Scholar
  • 8 Walz DA, Anderson GF, Ciaglowski RE, Aiken M, Fenton II JW. Thrombin-elicited contractile responses of aortic smooth muscle. Proc Soc Exp Biol Med 1985; 180: 518-526
    CrossrefPubMedSuche in Google Scholar
  • 9 Dodt J, Machleidt W, Seemüller U, Maschler R, Fritz H. Isolation and characterization of hirudin isoinhibitors and sequence analysis of hirudin PA. Biol Chem Hoppe-Seyler 1986; 367: 803-811
    PubMedSuche in Google Scholar
  • 10 Markwardt F. Hirudin as an inhibitor of thrombin. Methods Enzym 1970; 19: 924-932
    PubMedSuche in Google Scholar
  • 11 Stone SR, Hofsteenge J. Kinetics of the inhibition of thrombin by hirudin. Biochemistry 1986; 25: 4622-4628
    CrossrefPubMedSuche in Google Scholar
  • 12 Harvey RP, Degryse E, Stéfani L, Schamber F, Cazinave J-P, Courtney M, Tolstoshev P, Lecocq J-P. Cloning and expression of a cDNA coding for the anticoagulant hirudin from the bloodsucking leech, Hirudo medicinalis . Proc Natl Acad Sci 1986; 83: 1084-1088
    CrossrefPubMedSuche in Google Scholar
  • 13 Riehl-Bellon N, Carvallo D, Acker M, Dorsselaer AV, Marquet M, Loison G, Lemoine Y, Brown SW, Courtney M, Roitsch C. Purification and biochemical characterization of recombinant hirudin produced by Saccharomyces cerevisiae . Biochemistry 1989; 28: 2941-2949
    CrossrefPubMedSuche in Google Scholar
  • 14 Markwardt F. Pharmacology of hirudin: One hundred years after the first report of the anticoagulant agent in medicinal leeches. Biomed Biochim Acta 1985; 44: 1007-1013
    PubMedSuche in Google Scholar
  • 15 Markwardt F. Development of hirudin as an antithrombotic agent. Semin Thromb Hemostas 1989; 15: 269-282
    Thieme ConnectPubMedSuche in Google Scholar
  • 16 Johnson PH, Sze P, Winant R, Payne PW, Lazar JB. Biochemistry and genetic engineering of hirudin. Semin Thromb Hemostas 1989; 15: 302-315
    Thieme ConnectPubMedSuche in Google Scholar
  • 17 Hofsteenge J, Taguchi H, Stone SR. Effect of thrombomodulin on the kinetics of the interaction of thrombin with substrates and inhibitors. Biochem J 1986; 237: 243-251
    CrossrefPubMedSuche in Google Scholar
  • 18 Brown JE, Baugh RF, Hougie C. The inhibition of the intrinsic generation of activated factor X by heparin and hirudin. Thromb Res 1980; 17: 267-272
    CrossrefPubMedSuche in Google Scholar
  • 19 Rick ME, Hoyer LW. Thrombin activation of factor VIII the effect of inhibitors. Br J Haematol 1977; 36: 585-597
    CrossrefPubMedSuche in Google Scholar
  • 20 Tam SW, Fenton II JW, Detwiler TC. Dissociation of thrombin from platelets by hirudin. J Biol Chem 1979; 254: 8723-8725
    PubMedSuche in Google Scholar
  • 21 Bizios R, Lai L, Fenton II JW, Malik AB. Thrombin-induced chemotaxis and aggregation of neutrophils. J Cell Physiol 1986; 128: 485-490
    CrossrefPubMedSuche in Google Scholar
  • 22 Fenton II JW, Olson TA, Zabinski MP, Wilner GD. Anion-binding exosite of human a-thrombin and fibrin(ogen) recognition. Biochemistry 1988; 27: 7106-7112
    CrossrefPubMedSuche in Google Scholar
  • 23 Kaminski M, McDonagh J. Inhibited thrombins: Interactions with fibrinogen and fibrin. Biochem J 1987; 242: 881-887
    CrossrefPubMedSuche in Google Scholar
  • 24 Olson TA, Sonder SA, Wilner GD, Fenton II JW. Heparin binding in proximity to the catalytic site of human a-thrombin. Ann NY Acad Sci 1986; 485: 96-103
    CrossrefPubMedSuche in Google Scholar
  • 25 Chang J-Y. The hirudin-binding site of human a-thrombin. Identification of lysyl residues which participate in the combining site of hirudin-thrombin complex. J Biol Chem 1989; 264: 7141-7146
    PubMedSuche in Google Scholar
  • 26 Krstenansky JL, Mao SJT. Antithrombin properties of C-terminus of hirudin using synthetic unsulfated N-a-acetyl-hirudin45_65 . FEBS Lett 1987; 211: 10-16
    CrossrefPubMedSuche in Google Scholar
  • 27 Maraganore JM, Chao B, Joseph ML, Jablonski J, Ramachandran KL. Anticoagulant activity of synthetic hirudin peptides. J Biol Chem 1989; 264: 8692-8698
    PubMedSuche in Google Scholar
  • 28 Rydel TJ, Ravichandran KG, Tulinsky A, Bode W, Huber R, Roitsch C, Fenton II JW. The structure of a complex of recombinant hirudin and human a-thrombin. Science 1990; 249: 277-280
    CrossrefPubMedSuche in Google Scholar
  • 29 Grutter MG, Priestle JP, Rahuel J, Grossenbacher H, Bode W, Hofsteenge J, Stone SR. Crystal structure of the thrombin-hirudin complex: a novel mode of serine protease inhibition. EMBO J 1990; 9: 2361-2365
    PubMedSuche in Google Scholar
  • 30 Fenton II JW, Fasco MJ, Stackrow AB, Aronson DC, Young AM, Finlayson JS. Human thrombins: Production, evaluation, and properties of a-thrombin. J Biol Chem 1977; 252: 3587-3598
    PubMedSuche in Google Scholar
  • 31 Boyum A. Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Lab Invest 1968; 21 Suppl. (19) 77-89
    CrossrefPubMedSuche in Google Scholar
  • 32 Ribaudo RK, Kreutzer DL. Analysis of leukocyte migration and chemotaxis. In: Investigations of Cell Mediated Immunity. Academic Press, Inc.; New York: 1982. pp 116-125
    Suche in Google Scholar
  • 33 Hartley BS, Shotton DM. Pancreatic elastase. The Enzymes, III 1971; 323-373
    PubMedSuche in Google Scholar
  • 34 Bar-Shavit R, Kahn A, Mudd MS, Wilner GD, Mann KG, Fenton II JW. Localization of a chemotactic domain in human thrombin. Biochemistry 1984; 23: 397-400
    CrossrefPubMedSuche in Google Scholar
  • 35 Bode W, Mayr I, Baumann U, Huber R, Stone SR, Hofsteenge J. The refined 1.9 Â crystal structure of human a-thrombin interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment. EMBO J 1989; 8: 3467-3475
    CrossrefPubMedSuche in Google Scholar