PDF herunterladen
Thromb Haemost 1999; 82(02): 226-233
DOI: 10.1055/s-0037-1615837
Research Article
Schattauer GmbH

Activation of the Plasma Kallikrein/Kinin System on Cells: A Revised Hypothesis

Alvin H. Schmaier
1   Division of Hematology and Oncology, Departments of Internal Medicine and Pathology, University of Michigan, Ann Arbor, MI, USA
,
Rasmus Røjkjær
1   Division of Hematology and Oncology, Departments of Internal Medicine and Pathology, University of Michigan, Ann Arbor, MI, USA
,
Zia Shariat-Madar
1   Division of Hematology and Oncology, Departments of Internal Medicine and Pathology, University of Michigan, Ann Arbor, MI, USA
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
09. Dezember 2017 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Introduction

For the last 25 years, most investigators in the field of plasma kallikrein/kinin have accepted the contact activation hypothesis by factor XII initiates plasma kallikrein/kinin system activation by binding to a physiologic, negatively-charged surface. This hypothesis forms the basis of the common surface-based coagulation assays, such as the activated partial thromboplastin time (aPTT). Also, it may be the mechanism by which the plasma kallikrein/kinin system becomes activated in vivo when exposed to artificial surfaces, such as those used in medical interventions, and following infection.

A physiologic, negatively-charged surface, however, capable of initiating the activation of this system has never been convincingly described. This fact questions the role of this system in vivo. Sulfatides, phospholipids, cholesterol sulfate, chondroitin sulfate, heparins, and other glycosaminoglycans have been proposed as physiologic negatively charged surfaces. The autoactivation of factor XII, which can take several hours depending on the surface, leads to prekallikrein (PK) activation. Kallikrein formation reciprocally activates more factor XII in a reaction that is at least 1,000-fold faster than autoactivation. In addition to the surface, the rate of initiation and amplification of this system is accelerated by high molecular weight kininogen (HK). Activation of the zymogens factor XII and PK result in enzymes that have been proposed to contribute to factor XI activation (coagulation), complement activation, bradykinin (BK) liberation, fibrinolysis, and granulocyte activation in vitro.

It is well known, however, that clinical deficiencies in factor XII, PK, and HK are not associated with bleeding, even though these deficiencies markedly prolong surfaced-activated coagulation assays for hemostasis. This information indicates that this system contributes little, if anything, to hemostasis. Recently, this field has been thoroughly reviewed.1,2 The purpose of this report is to present a new hypothesis for assembly and activation of this system on viable cell membranes and to begin to clarify these proteins’ roles in vivo.

Over 10 years ago, our laboratory developed a working hypothesis to serve as an alternative to the factor XII autoactivation mechanism for the initiation of activation of the proteins of the plasma kallikrein/kinin system. We reasoned that, in vivo, it is the assembly of a multiprotein complex of these proteins on cell receptors that allows for localization and activation of this system. To prove that hypothesis, we sought to accomplish the following three things. First, we attempted to determine whether there is a receptor(s) for the proteins of this system on cell membranes. Second, we sought to show whether the assembly of the proteins of the plasma kallikrein/kinin system on cell membranes results in activation of PK and factor XII. Finally, we attempted to demonstrate biological activities associated with the activation of these proteins on cell membranes. The following report details this work and characterizes a new hypothesis for the assembly and activation of the proteins of the plasma kallikrein/kinin system.

 

  • References

  • 1 Colman RW, Schmaier AH. Contact system: a vascular biology modulator with anticoagulant, profibrinolytic, antiadhesive, and proinflammatory attributes. Blood 1997; 90: 3819-3843.
    PubMedSuche in Google Scholar
  • 2 Schmaier AH. Contact activation. In: Loscalzo J, Shafer A. eds. Thrombosis and Hemorrhage. 2nd edition. Baltimore: Williams & Wilkins; 1998: 105-127.
    Suche in Google Scholar
  • 3 Hasan AAK, Cines DB, Ngaiza JR, Jaffe E, Schmaier AH. High molecular weight kininogen is exclusively membrane bound on endothelial cells to influence activation of vascular endothelium. Blood 1995; 85: 3134-3143.
    PubMedSuche in Google Scholar
  • 4 Zini JM, Schmaier AH, Cines DB. Bradykinin regulates the expression of kininogen binding sites on endothelial cells. Blood 1993; 81: 2936-2946.
    PubMedSuche in Google Scholar
  • 5 Motta G, Røjkjær R, Hasan AAK, Cines DB, Schmaier AH. High molecular weight kininogen regulates prekallikrein assembly and activation on endothelial cells: a novel mechanism for contact activation. Blood 1998; 91: 516-528.
    PubMedSuche in Google Scholar
  • 6 Røjkjær R, Hasan AAK, Schmaier AH. A novel mechanism for factor XI activation on endothelial cells independent of autoactivation, α-thrombin, or factor XIIa. Blood 1998; 92 (Suppl. 01) 40a.
    PubMedSuche in Google Scholar
  • 7 Hasan AAK, Zisman T, Schmaier AH. Identification of cytokeratin 1 as a binding protein and presentation receptor for kininogens on endothelial cells. Proc Natl Acad Sci USA. 1998; 95: 3615-3620.
    CrossrefPubMedSuche in Google Scholar
  • 8 Shariat-Madar A, Mahdi F, Schmaier AH. Mapping the kininogen binding site on cytokeratin 1. J Biol Chem. 1999; 274: 7137-7145.
    CrossrefPubMedSuche in Google Scholar
  • 9 Herwald H, Hasan AAK, Godovac-Zimmermann J, Schmaier AH, Muller-Esterl W. Identification of an endothelial cell binding site on kininogens’ domain 3. J Biol Chem. 1995; 270: 14634-14642.
    PubMedSuche in Google Scholar
  • 10 Hasan AAK, Cines DB, Herwald H, Schmaier AH, Muller-Esterl W. Mapping the cell binding site on high molecular weight kininogen’s domain 5. J Biol Chem. 1995; 270: 19256-19261.
    CrossrefPubMedSuche in Google Scholar
  • 11 Wachtfogel YT, DeLa Cadena RA, Kunapuli SP, Rick L, Miller M, Schultze RL, Altieri DC, Edgington TS, Colman RW. High molecular weight kininogen binds to Mac-1 on neutrophils by its heavy chains (domain 3) and its light chain (domain 5). J Biol Chem. 1988; 269: 19307-19312.
    PubMedSuche in Google Scholar
  • 12 Colman RW, Pixley RA, Najamunnisa S, Yan W-Y, Wang J, Mazar A, McCrae KR. Binding of high molecular weight kininogen to human endothelial cells is mediated via a site within domains 2 and 3 of the urokinase receptor. J Clin Invest. 1997; 100: 1481-1487.
    CrossrefPubMedSuche in Google Scholar
  • 13 Kindzelskii AL, Laska ZO, Todd III RF, Petty HR. Urokinase-type plasminogen activator receptor reversibly dissociates from complement receptor type 3 (αMβ2, CD11b/CD18) during neutrophil polarization. J Immunol. 1996; 156: 297-309.
    PubMedSuche in Google Scholar
  • 14 Wei Y, Lukashev M, Simon DI, Bodary SC, Rosenberg S, Doyle MV, Chapman HA. Regulation of integrin function by the urokinase receptor. Science 1996; 273: 1551-1555.
    CrossrefPubMedSuche in Google Scholar
  • 15 Herwald H, Dedio J, Kellner R, Loos M, Mueller-Esterl W. Isolation and characterization of the kininogen-binding protein p33 from endothelial cells: identity with the gC1q receptor. J Biol Chem. 1996; 271: 13040-13047.
    CrossrefPubMedSuche in Google Scholar
  • 16 Joseph K, Ghebrehiwet B, Peerschke EIB, Reid KBM, Kaplan AP. Identification of the zinc-dependent endothelial cell binding protein for high molecular weight kininogen and factor XII: identity with the receptor that binds to the globular “heads” of C1q (gC1qR). Proc Natl Acad Sci USA. 1996; 93: 8552-8557.
    CrossrefPubMedSuche in Google Scholar
  • 17 Dedio J, Mueller-Esterl W. Kininogen binding protein p33/gC1qR is localized in the vesicular fraction of endothelial cells. FEBS Lett. 1996; 399: 255-2558.
    CrossrefPubMedSuche in Google Scholar
  • 18 Dedio J, Jahnen-Dechent W, Bachmann M, Muller-Esterl W. The multiligand-binding protein gC1qR, putative C1q receptor, is a mitochondrial protein. J Immunol. 1998; 160: 3534-3542.
    PubMedSuche in Google Scholar
  • 19 Van den Berg RH, Prins F, Faber-Krol MC, Lynch NJ, Schwarble W, Van Es LA, Daha MR. Intracellular localization of the human receptor for globular domains of C1q. J Immunol. 1998; 158: 3909-3916.
    PubMedSuche in Google Scholar
  • 20 Hasan AAK, Krishnan R, Tulinsky A, Srikanth S, Schmaier AH. The mechanism of thrombostatin’s inhibition of thrombin-induced platelet activation. Circulation. 1998; (Suppl. 01) I-800.
    PubMedSuche in Google Scholar
  • 21 Meloni FJ, Schmaier AH. Low molecular weight kininogen binds to platelets to modulate thrombin-induced platelet activation. J Biol Chem. 1991; 266: 6786-6794.
    PubMedSuche in Google Scholar
  • 22 Puri RN, Zhou F, Hu CJ, Colman RF, Colman RW. High molecular weight kininogen inhibits thrombin-induced platelet aggregation and cleavage of aggregin by inhibiting binding of thrombin to platelets. Blood 1991; 77: 500-507.
    PubMedSuche in Google Scholar
  • 23 Bradford HN, DeLa Cadena RA, Kunapuli SP, Dong JF, Lopez JA, Colman RW. Human kininogens regulate thrombin binding to platelets through GPIb-IX complex. Blood 1997; 90: 1508-1515.
    PubMedSuche in Google Scholar
  • 24 Colman RW, Lin Y, Johnson D, Mousa SA. Inhibition of angiogenesis by peptides derived from kininogen. Blood 1998; 92 (Suppl. 01) 174a.
    PubMedSuche in Google Scholar
  • 25 Røjkjær R, Motta G, Hasan AAK, Schousboe I, Schmaier AH. Factor XII does not initiate prekallikrein activation on endothelial cells. Thromb Haemost. 1998; 80: 74-81.
    Thieme ConnectPubMedSuche in Google Scholar
  • 26 Bock PE, Shore JD, Tans G, Griffin JH. Protein-protein interactions in contact activation of blood coagulation. Binding of high molecular weight kininogen and the 5-(iodoacetamido) fluorescein-labeled kininogen light chain to prekallikrein, kallikrein, and the separated kallikrein heavy and light chains. J Biol Chem. 1985; 260: 12434-12443.
    PubMedSuche in Google Scholar
  • 27 Lin Y, Harris RB, Yan W, McCrae KR, Zhang H, Colman RW. High molecular weight kininogen peptides inhibit the formation of kallikrein on endothelial cell surfaces and subsequent urokinase-dependent plasmin formation. Blood 1997; 90: 690-697.
    PubMedSuche in Google Scholar
  • 28 Røjkjær R, Schmaier AH. Activation of the plasma kallikrein/kinin system on endothelial cells. Proc Assoc Am Physicians. 1999; 111: 220-227.
    CrossrefPubMedSuche in Google Scholar
  • 29 Berretini M, Schleef R, Heeb MJ, Hopmeier P, Griffin JH. Assembly and expression of an intrinsic factor IX activator complex on the surface of cultured human endothelial cells. J Biol Chem. 1992; 267: 19833-19839.
    PubMedSuche in Google Scholar
  • 30 Stern DM, Nossel HL, Owen J. Acquired antibody to factor XI in a patient with congenital factor XI deficiency. J Clin Invest. 1982; 69: 1270-1276.
    CrossrefPubMedSuche in Google Scholar
  • 31 DeLa Cadena RA, Baglia FA, Johnson CA, Walsh PN, Colman RW. Naturally occurring human antibodies against two distinct functional domains in the heavy chain of FXI/FXIa. Blood 1988; 72: 1748-1754.
    PubMedSuche in Google Scholar
  • 32 Crutchley DJ, Ryan JW, Ryan US, Fisher GH. Bradykinin-induced release of prostacyclin and thromboxanes from bovine pulmonary artery endothelial cells. Biochim Biophys Acta. 1983; 751: 99-107.
    CrossrefPubMedSuche in Google Scholar
  • 33 Hong SL. Effect of bradykinin and thrombin on prostacyclin synthesis in endothelial cells from calf and pig aorta and human umbilical cord vein. Thromb Res. 1980; 18: 787-795.
    CrossrefPubMedSuche in Google Scholar
  • 34 Holland JA, Pritchard KA, Pappolla MA, Wolin MS, Rogers NJ, Stemerman MB. Bradykinin induces superoxide anion release from human endothelial cells. J Cell Physiol. 1990; 143: 21-25.
    CrossrefPubMedSuche in Google Scholar
  • 35 Smith D, Gilbert M, Owen WG. Tissue plasminogen activator release in vivo in response to vasoactive agents. Blood 1983; 66: 835-839.
    PubMedSuche in Google Scholar
  • 36 Brown NJ, Nadeau JH, Vaughan DE. Selective stimulation of tissue-type plasminogen activator (t-PA) in vivo by infusion of bradykinin. Thromb Haemost. 1997; 77: 522-525.
    Thieme ConnectPubMedSuche in Google Scholar
  • 37 Palmer RMJ, Ferrige AG, Moncada S. Nitric oxide release accounts for the biologic activity of endothelium-derived relaxing factor. Nature 1987; 372: 524-526.
    PubMedSuche in Google Scholar
  • 38 Nakashima M, Mombouli JV, Taylor AA, Vanhoutte PM. Endothelium-dependent hyperpolarization caused by bradykinin in human coronary arteries. J Clin Invest. 1993; 92: 2867-2871.
    CrossrefPubMedSuche in Google Scholar
  • 39 Gurewich V, Johnson M, Loza JP, Pannell R. Pro-urokinase and prekallikrein are both associated with platelets. Implications for the intrinsic pathway of fibrinolysis and for therapeutic thrombolysis. FEBS Lett. 1993; 318: 317-321.
    CrossrefPubMedSuche in Google Scholar
  • 40 Loza JP, Gurewich V, Johnstone M, Pannell R. Platelet-bound prekallikrein promotes pro-urokinase-induced clot lysis: a mechanism for targeting the factor XII dependent intrinsic pathway of fibrinolysis. Thromb Haemost. 1994; 71: 347-352.
    Thieme ConnectPubMedSuche in Google Scholar
  • 41 Lenich C, Pannell R, Gurewich V. Assembly and activation of the intrinsic fibrinolytic pathway on the surface of human endothelial cells in culture. Thromb Haemost. 1995; 74: 698-703.
    Thieme ConnectPubMedSuche in Google Scholar
  • 42 Puri RN, Matsueda R, Umeyama H, Bradford H, Colman RW. Modulation of thrombin-induced platelet aggregation by inhibition of calpain by a synthetic peptide derived from the thiol-protease inhibitory sequence of kininogens and S-(3-nitro-2-pyridinesulfenyl)-cysteine. Eur J Biochem. 1993; 214: 233-241.
    CrossrefPubMedSuche in Google Scholar
  • 43 Hasan AAK, Amenta S, Schmaier AH. Bradykinin and its metabolite, Arg-Pro-Pro-Gly-Phe, are selective inhibitors of α-thrombin-induced platelet activation. Circulation. 1996; 94: 1465-1473.
    CrossrefPubMedSuche in Google Scholar