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Thromb Haemost 2000; 83(06): 874-881
DOI: 10.1055/s-0037-1613936
Commentary
Schattauer GmbH

A Monoclonal Antibody Raised against Human β-factor XIIa which also Recognizes α-factor XIIa but not Factor XII or Complexes of Factor XIIa with C1 Esterase Inhibitor

M. Peter Esnouf
1   From the Nuffield Department of Clinical Biochemistry, University of Oxford, The Radcliffe Infirmary, Oxford, UK
,
Annette I. Burgess
1   From the Nuffield Department of Clinical Biochemistry, University of Oxford, The Radcliffe Infirmary, Oxford, UK
,
Alister W. Dodds
2   MRC Immunochemistry Unit, Oxford, UK
,
Anna F. Sarphie
1   From the Nuffield Department of Clinical Biochemistry, University of Oxford, The Radcliffe Infirmary, Oxford, UK
,
George J. Miller
3   MRC Epidemiology and Medical Care Unit, The Wolfson Institute of Preventive Medicine, London, UK
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Publikationsverlauf

Received 19. Juli 1999

Accepted after resubmission 29. Januar 2000

Publikationsdatum:
14. Dezember 2017 (online)

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Summary

A monoclonal antibody (mAb 2/215) against human β-factor XIIa (β-FXIIa), was shown by equilibrium binding studies to have a high affinity for α-factor XIIa (α-FXIIa) (Kd 1.8 nM) and β-FXIIa (Kd 0.65 nM) but no detectable reaction with FXII zymogen or α - esterase inhibitor (C1-INH) complex. Surface plasmon resonance studies showed that the mAb 2/215 bound to immobilized α-FXIIa with high affinity (KD 3.93 ± 1.46 × 10−11 M). Western blots employing mAb 2/215 indicated that human plasma contained small amounts of α-FXIIa but no β-FXIIa. mAb 2/215 did not inhibit the amidolytic activity of β-FXIIa and protected β-FXIIa from inhibition by C1-INH. The recovery by ELISA ,employing mAb 2/215 as the capture antibody, of α-FXIIa added to plasma was 11.3%, 42% after inhibition of α-FXIIa with 3:4dichloroisocoumarin, and 82% when 0.5% TritonX100 was added to the assay. Gel filtration showed that the majority of plasma α-FXIIa existed as a complex (Mr ∼170000). This distinctive mAb increases the capacity to study the contact system in health and disease.

Key words

Monoclonal antibody - factor XIIa - ELISA - affinity binding studies
 

  • References

  • 1 Ratnoff OD, Saito H. Interactions among Hageman factor, plasma prekallikrein, high molecular weight kininogen, and plasma thromboplastin antecedent. Proc Natl Acad Sci USA 1979; 76: 958-61.
    CrossrefPubMedGoogle Scholar
  • 2 Tans G, Rosing J, Griffin JH. Sulfatide-dependent autoactivation of human blood coagulation Factor XII (Hageman Factor). J Biol Chem 1983; 258: 8215-22.
    PubMedGoogle Scholar
  • 3 Small EJ, Katzmann JA, Tracy RP, Ratnoff OD, Goldsmith Jr. GH, Everson B. A monoclonal antibody that inhibits activation of human Hageman factor (factor XII). Blood 1985; 65: 202-10.
    PubMedGoogle Scholar
  • 4 Saito H, Ishihara T, Suzuki H, Watanabe T. Production and characterization of a murine monoclonal antibody against a heavy chain of Hageman factor (factor XII). Blood 1985; 65: 1263-8.
    CrossrefPubMedGoogle Scholar
  • 5 Clarke BJ, Cote HC, Cool DE, Clark ILewis, Saito H, Pixley RA, Colman RW, MacGillivray RT. Mapping of a putative surface-binding site of human coagulation factor XII. J Biol Chem 1989; 264: 11497-502.
    PubMedGoogle Scholar
  • 6 Pixley RA, Colman RW. A monoclonal antibody recognizing an iscosapeptide sequence in the heavy chain of human factor XII inhibits surfacecatalyzed activation. Adv Exp Med Biol 1989; 247a: 473-6.
    PubMedGoogle Scholar
  • 7 Nuijens JH, Huijbregts CC, Eerenberg AJBelmer, Meijers JC, Bouma BN, Hack CE. Activation of the contact system of coagulation by a monoclonal antibody directed against a neodeterminant in the heavy chain region of human coagulation factor XII (Hageman factor). J Biol Chem 1989; 264: 12941-9.
    PubMedGoogle Scholar
  • 8 Ravon DM, Citarella F, Lubbers YT, Pascucci B, Hack CE. Monoclonal antibody F1 binds to the kringle domain of factor XII and induces enhanced susceptibility for cleavage by kallikrein. Blood 1995; 86: 4134-43.
    CrossrefPubMedGoogle Scholar
  • 9 Lachmann PJ, Strangeways L, Vyakarnam A, Evan G. Raising antibodies by coupling peptides to PPD and immunizing BCG-sensitized animals. Ciba Found Symp 1986; 119: 25-57.
    PubMedGoogle Scholar
  • 10 Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 1975; 256: 495-7.
    CrossrefPubMedGoogle Scholar
  • 11 Ford RP, Esnouf MP, Burgess AI, Sarphie AF. An enzyme linked immunoabsorbent assay (ELISA) for the measurement of activated factor XII (Hageman factor) in human plasma. J. Immunoassay 1996; 17: 119-31.
    PubMedGoogle Scholar
  • 12 Fujikawa K, Davie EW. Human factor XII (Hageman factor). Methods Enzymol 1981; 80 Pt C: 198-211.
    PubMedGoogle Scholar
  • 13 Kohn J, Wilchek M. A new approach (cyano-transfer) for cyanogen bromide activation of Sepharose at neutral pH, which yields activated resins, free of interfering nitrogen derivatives. Biochem Biophys Res Commun 1982; 107: 878-84.
    CrossrefPubMedGoogle Scholar
  • 14 Fujikawa K, McMullen BA. Amino acid sequence of human beta-factor XIIa. J Biol Chem 1983; 258: 10924-33.
    PubMedGoogle Scholar
  • 15 Jameson GW, Roberts DV, Adams RW, Kyle WS, Elmore DT. Determination of the operational molarity of solutions of bovine alpha-chymotrypsin, trypsin, thrombin and factor Xa by spectrofluorimetric titration. Biochem J 1973; 131: 107-17.
    CrossrefPubMedGoogle Scholar
  • 16 Sim RB, Reboul A. Preparation and properties of human C1 inhibitor. Methods Enzymol 1981; 80 Pt C: 43-54.
    PubMedGoogle Scholar
  • 17 Proctor RR, Rapaport SI. The partial thromboplastin time with kaolin:a simple screening test for the first stage plasma clotting deficiencies. Am J Clin Pathol 1961; 35: 212-9.
    PubMedGoogle Scholar
  • 18 Friguet B, Chaffotte AF, Djavadi LOhaniance, Goldberg ME. Measurements of the true affinity constant in solution of antigen-antibody complexes by enzyme-linked immunosorbent assay. J Immunol Methods 1985; 77: 305-19.
    CrossrefPubMedGoogle Scholar
  • 19 Kam CM, Fujikawa K, Powers JC. Mechanism-based isocoumarin inhibitors for trypsin and blood coagulation serine proteases: new anticoagulants. Biochemistry 1988; 27: 2547-57.
    CrossrefPubMedGoogle Scholar
  • 20 Burnette WN. “Western blotting”: electrophoretic transfer of proteins from sodium dodecyl sulfate-polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem 1981; 112: 195-203.
    CrossrefPubMedGoogle Scholar
  • 21 Knecht DA, Dimond RL. Visualization of antigenic proteins on Western blots. Anal Biochem 1984; 136: 180-4.
    CrossrefPubMedGoogle Scholar
  • 22 Saito H. The contact phase of blood coagulation. In: Bloom AL, Forbes CD, Thomas DP, Tuddenham EGD. eds. Haemostasis and Thrombosis. 3rd ed. London: Churchill Livingstone; 1994: 289 vol 1.
    Google Scholar
  • 23 Cool DE, Edgell CJ, Louie GV, Zoller MJ, Brayer GD, MacGillivray RT. Characterization of human blood coagulation factor XII cDNA. Prediction of the primary structure of factor XII and the tertiary structure of beta-factor XIIa. J Biol Chem 1985; 260: 13666-76.
    PubMedGoogle Scholar
  • 24 Munakata M, Komiyama Y, Mori T, Okuda K, Murakami T, Masuda M, Egawa H, Takahashi H. Evaluation of the factor XIIa assay kit. Rinsho-Byori 1996; 44: 883-8.
    PubMedGoogle Scholar
  • 25 Pixley RA, Schapira M, Colman RW. The regulation of human factor XIIa by plasma proteinase inhibitors. J Biol Chem 1985; 260: 1723-9.
    PubMedGoogle Scholar
  • 26 Cardigan RA, Donohoe S, Purdy G, Mackie IJ, Machin SJ. The association of factor VIIa, factor XIIa and beta2-glycoprotein-1 with triglyceride-rich lipoproteins in normolipidaemic subjects. Blood Coagul Fibrinolysis 1998; 09: 323-32.
    CrossrefPubMedGoogle Scholar
  • 27 Boisclair MD, Lane DA, Philippou H, Esnouf MP, Sheikh S, Hunt B, Smith KJ. Mechanisms of thrombin generation during surgery and cardiopulmonary bypass. Blood 1993; 82: 3350-7.
    PubMedGoogle Scholar
  • 28 Coppola R, Cristilli P, Cugno M, Ariens RA, Mari D, Mannucci PM. Measurement of activated factor XII in health and disease. Blood Coagul Fibrinolysis 1996; 07: 530-5.
    CrossrefPubMedGoogle Scholar
  • 29 Cugno M, Cicardi M, Bottasso B, Coppola R, Paonessa R, Mannucci PM, Agostini A. Activation of the coagulation cascade in C1-inhibitor deficiencies. Blood 1997; 89: 3213-8.
    PubMedGoogle Scholar
  • 30 Miller GJ, Esnouf MP, Burgess AI, Cooper JA, Mitchell JP. Risk of Coronary Heart Disease and activation of Factor XII in Middle-Aged Men. Arterioscler Thromb Vasc Biol 1997; 17: 2103-6.
    CrossrefPubMedGoogle Scholar
  • 31 Kohler HP, Carter AM, Stickland MH, Grant PJ. Levels of activated FXII in survivors of myocardial infarction-association with circulating risk factors and extent of coronary artery disease. Thromb Haemost 1998; 79: 14-8.
    Artikel in Thieme ConnectPubMedGoogle Scholar