Download PDF
Thromb Haemost 1996; 75(04): 578-584
DOI: 10.1055/s-0038-1650325
Original Article
Schattauer GmbH Stuttgart

Infusion of Phospholipid Vesicles Amplifies the Local Thrombotic Response to TNF and Anti-Protein C into a Consumptive Response

F B Taylor Jr.
1   The Oklahoma Medical Research Foundation, Oklahoma City, USA
,
S E He
1   The Oklahoma Medical Research Foundation, Oklahoma City, USA
,
A C K Chang
2   University of Oklahoma Health Sciences Center, Oklahoma City, USA
,
J Box
3   Howard Hughes Medical Institute, Oklahoma City, USA
,
G Ferrell
1   The Oklahoma Medical Research Foundation, Oklahoma City, USA
,
D Lee
1   The Oklahoma Medical Research Foundation, Oklahoma City, USA
,
M Lockhart
1   The Oklahoma Medical Research Foundation, Oklahoma City, USA
,
G Peer
2   University of Oklahoma Health Sciences Center, Oklahoma City, USA
,
C T Esmon
1   The Oklahoma Medical Research Foundation, Oklahoma City, USA
2   University of Oklahoma Health Sciences Center, Oklahoma City, USA
3   Howard Hughes Medical Institute, Oklahoma City, USA
› Author Affiliations
Further Information

Publication History

Received 19 September 1995

Accepted after resubmission 05 January 1996

Publication Date:
10 July 2018 (online)

  PDF Download  Permissions and Reprints

Summary

Inflammation often is considered a contributing factor to both thrombosis and disseminated intravascular coagulation. The molecular mechanisms that dictate which of these clinical manifestations will result from the inflammatory stimulus remain obscure. Bacterial infection and certain tumors are common initiators of the disseminated intravascular coagulant response. Complement activation resulting from bacterial infection shares with selected tumors the capacity to generate or release membrane particles that lack functional adhesion receptors and hence could circulate to amplify a disseminated intravascular coagulant response. We developed a model of venous thrombosis that resulted in localized thrombus formation without disseminated intravascular coagulation. The model involves infusion of tumor necrosis factor, blockade of protein C and a partial decrease in venous flow caused by ligation of the superficial femoral vein without obstruction of the deep femoral vein. Infusion of phospholipid vesicles into this model resulted in amplification of a localized thrombotic response into a consumptive response.

Seven different groups of animals were studied. The first three groups established the conditions necessary to produce deep vein thrombosis. The second four groups established the conditions necessary to produce disseminated intravascular coagulation. The infusion of phospholipid vesicles plus tumor necrosis factor and anti-protein C antibody resulted in consumption of fibrinogen, the production of thrombin/antithrombin complexes, a fall in platelet count, and venous thrombosis. Without ligation and catheterization phospholipid vesicles failed to produce the consumptive response. We conclude, therefore, that phospholipid vesicles can amplify a local thrombotic response into a consumptive response, and that vesiculation accompanying inflammation is one means by which localized coagulant activity may be amplified to produce disseminated intravascular coagulation.

 

  • References

  • 1 Nawroth PP, Stem DM. Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J Exp Med 1986; 163: 740-745
    CrossrefPubMedGoogle Scholar
  • 2 Moore KL, Esmon CT, Esmon NL. Tumor necrosis factor leads to internalization and degradation of thrombomodulin from the surface of bovine aortic endothelial cells in culture. Blood 1989; 73: 159-165
    PubMedGoogle Scholar
  • 3 Comp PC, Doray D, Patton D, Esmon CT. An abnormal plasma distribution of protein S occurs in functional protein S deficiency. Blood 1986; 67: 504-508
    PubMedGoogle Scholar
  • 4 Colucci M, Paramo JA, Collen D. Generation in plasma of fast-acting inhibitor of plasminogen activator in response to endotoxin stimulation. J Clin Invest 1985; 75: 818-821
    CrossrefPubMedGoogle Scholar
  • 5 McEver R. Role of endothelium in the inflammatory response. In: Critical Care Shoemaker WC, Taylor RW. eds. The Society of Critical Medicine. State of the Art, 12th Edition; Fullerton, CA: 1991: 121-141
  • 6 Taylor Jr FB, Esmon CT, Chang A. Primate model of deep vein thrombosis induced by inflammatory mediators. Circulation 1990 82. III-770 (abstr).
    PubMedGoogle Scholar
  • 7 Wakefield TW, Wrobleski SK, Sarpa MS, Taylor Jr FB, Esmon CT, Cheng A, Greenfield LJ. Deep venous thrombosis in the baboon: An experimental model. J Vase Surg 1991; 14: 588-598
    CrossrefPubMedGoogle Scholar
  • 8 Taylor Jr FB, Hoogendoom H, Chang ACK, Peer G, Nesheim ME, Catlett R, Stump DC, Giles AR. Anticoagulant and fibrinolytic activities are promoted, not retarded, in vivo after thrombin generation in the presence of a monoclonal antibody that inhibits activation of protein C. Blood 1992; 79: 1720-1728
    PubMedGoogle Scholar
  • 9 Sack Jr GH, Levin J, Bell WR. Trousseau’s syndrome and other manifestations of chronic disseminated coagulopathy in patients with neoplasms: Clinical, pathologic, and therapeutic features. (Baltimore) Medicine 1977; 56: 1-13
    CrossrefPubMedGoogle Scholar
  • 10 Neame PB, Kelton JG, Walker IR, Stewart IO, Nossel HL, Hirsh J. Thrombocytopenia in septicemia: The role of disseminated intravascular coagulation. Blood 1980; 56: 88-94
    PubMedGoogle Scholar
  • 11 Srichaikul TS, Nimmanitaya N, Artchararit T, Siriasawakul T, Sungpeuk P. Fibrinogen metabolism and disseminated intravascular coagulation in Dengue Hemorrhagic Fever. Am J Trop Med Hygiene 1977; 26 (03) 525-531
    PubMedGoogle Scholar
  • 12 Dvorak HF, Van De Water L, Bitzer AM, Dvorak AM, Anderson D, Harvey VS, Bach R, Davis GL, De Wolf W, Carvalho ACA. Procoagulant activity associated with plasma membrane vesicles shed by cultured tumor cells. Cancer Res 1983; 43: 4434-4443
    PubMedGoogle Scholar
  • 13 Dvorak HF, Quay SC, Orenstein NS, Dvorak AM, Hahn P, Bitzer AM. Tumor shedding and coagulation. Science 1981; 212: 923-927
    CrossrefPubMedGoogle Scholar
  • 14 de Boer JP, Creasey AA, Chang A, Roem D, Eerenberg AJM, Hack CE, Taylor Jr FB. Activation of the complement system in baboons challenged with live Escherichia coli: Correlation with mortality and evidence for a biphasic activation pattern. Infect Immun 1993; 61 (10) 4293-4301
    PubMedGoogle Scholar
  • 15 Bokisch VA, Top Jr FH, Russell PK, Dixon FJ, Muller-Eberhard HJ. The potential pathogenic role of complement in Dengue Hemorrhagic Shock Syndrome. N Engl J Med 1973; 289: 996-1003
    CrossrefPubMedGoogle Scholar
  • 16 Sims PJ, Faioni EM, Wiedmer T, Shattil SJ. Complement proteins C5b-9 cause release of membrane vesicles from the platelet surface that are enriched in the membrane receptor for coagulation factor Va and express prothrombinase activity. J Biol Chem 1988; 263: 18205-8212
    PubMedGoogle Scholar
  • 17 Wiedmer T, Esmon CT, Sims PJ. Complement proteins C5b-9 stimulate procoagulant activity through platelet prothrombinase. Blood 1986; 68: 875-880
    PubMedGoogle Scholar
  • 18 Ando B, Wiedmer T, Hamilton KK, Sims PJ. Complement protein C5b-9 initiates secretion of platelet storage granules without increased binding of fibrinogen on von Willebrand factor to newly expressed cell surfaces GPIIb-IIIa. J Biol Chem 1988; 263: 11907-11914
    PubMedGoogle Scholar
  • 19 Owen WG, Esmon CT, Jackson CM. The conversion of prothrombin to thrombin. Characterization of the reaction products formed during the activation of bovine prothrombin. J Biol Chem 1974; 249: 594-605
    PubMedGoogle Scholar
  • 20 Steams DJ, Kurosawa S, Sims PJ, Esmon NL, Esmon CT. The interaction of a Ca2+-dependent monoclonal antibody with the protein C activation peptide region: Evidence for obligatory Ca2+ binding to both antigen and antibody. J Biol Chem 1988; 263: 826-832
    PubMedGoogle Scholar
  • 21 Steams DJ, Kurosawa S, Esmon CT. Micro-thrombomodulin: Residue 310-486 from the epidermal growth factor precursor-homology domain of thrombomodulin will accelerate protein C activation. J Biol Chem 1989; 264: 3352-3356
    PubMedGoogle Scholar
  • 22 Taylor Jr FB, Chang A, Esmon CT, D’Angelo A, Vigano-D’Angelo S, Blick KE. Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon. J Clin Invest 1987; 79: 918-925
    CrossrefPubMedGoogle Scholar
  • 23 Hanson SR, Griffin JH, Harker LA, Kelly AB, Esmon CT, Gruber A. Antithrombotic effects of thrombin-induced activation of endogenous protein C in primates. J Clin Invest 1993; 92: 2003-2012
    CrossrefPubMedGoogle Scholar
  • 24 Rezaie AR, Fiore EM, Neuenschwander PF, Esmon CT, Morrissey JH. Expression and purification of a soluble tissue factor fusion protein with an epitope for an unusual calcium-dependent antibody. Protein Exp Purif 1992; 3: 453-460
    CrossrefPubMedGoogle Scholar
  • 25 Barenholz Y, Gibbes D, Litman BJ, Goll J, Thompson D, Carlson FD. A simple method for the preparation of homogeneous phospholipid vesicles. Biochem J 1977; 16: 2806-2811
    CrossrefPubMedGoogle Scholar
  • 26 Hougie C. Methods for estimating fibrinogen concentration, thrombin time test. In: Hematology Williams WJ, Beutler E, Erslev AJ, Lichtman MA. eds. McGraw-Hill, New York, NY: 1983: 1667
  • 27 Wellcome Research Laboratories. Fibrinogen degradation products Thrombo-Wellcotest (rapid latex kit). Purley, Surrey, UK: Southern Press; 1984
  • 28 Gretch DR, Suter M, Stinski MF. The use of biotinylated monoclonal antibodies and streptavidin affinity chromatography to isolate herpes virus. Anal Biochem 1987; 163: 270-277
    CrossrefPubMedGoogle Scholar
  • 29 Esmon CT, Taylor Jr FB, Snow TR. Inflammation and coagulation: Linked processes potentially regulated through a common pathway mediated by protein C. Thromb Haemost 1991; 66: 160-165
    Article in Thieme ConnectPubMedGoogle Scholar
  • 30 Beutler B, Cerami A. The history, properties, and biological effects of cachectin. Biochemistry 1988; 27: 7575-7582
    CrossrefPubMedGoogle Scholar
  • 31 Comp PC, Esmon CT. Recurrent venous thromboembolism in patients with partial deficiency of protein S. N Engl J Med 1984; 311: 1525-1528
    CrossrefPubMedGoogle Scholar
  • 32 Loike JD, Silverstein R, Wright SD, Weitz JI, Huang AJ, Silverstein SC. The role of protected extracellular compartments in interactions between leukocytes, and platelets, and fibrin/fibrinogen matrices. Annals of New York Academy of Science 1992; 667: 167-173
    PubMedGoogle Scholar
  • 33 Northeast ADR, Bumand KG. The response of the vessel wall to thrombosis: The in vivo study of venous thrombolysis. Annals of New York Academy of Science 1992; 667: 127-150
    CrossrefPubMedGoogle Scholar
  • 34 Peerschke EIB, Reid KBM. Induction of Alphallb/Beta integrins (GPIIb-IIIa) and expression of procoagulant activity. Thromb Haemost 1993; 69 (06) 785 (abstr).
    PubMedGoogle Scholar
  • 35 Gemmell CH, Sefton MV, Yeo EL. Human platelet microparticle generation requires platelet bound fibrinogen: Ligand fidelity of GPIIb-IIIa. Thromb Haemost 1993; 69 (06) 700 (abstr).
    PubMedGoogle Scholar
  • 36 Zimmerman TS, Muller-Eberhard HJ. Blood coagulation initiation by a complement-mediated pathway. J Exp Med 1971; 134: 1601-1607
    CrossrefPubMedGoogle Scholar
  • 37 Holme PA, Solum NO, Brosstad F. Clinical significance of platelet-derived microvesicles, demonstration of their presence in patients suffering from disseminated intravascular coagulation (DIC). Thromb Haemost 1993; 69 (06) 1198 (abstr).
    PubMedGoogle Scholar
  • 38 Galli M, Grassi A, Barbui T. Platelet-derived micro vesicles in patients with antiphospholipid antibodies. Thromb Haemost 1993; 69 (06) 541 (abstr).
    PubMedGoogle Scholar
  • 39 Warkentin TE, Hayward CPM, Santos AV, Kelton JG. Platelet-derived microparticles are found in vivo in patients with heparin-induced thrombocytopenia. Thromb Haemost 1993; 69 (06) 912 (abstr)
    PubMedGoogle Scholar
  • 40 He S, Hinshaw L, Emerson T, Kosanke S, White G, Randolph MM, Chang ACK, Duerr M, Peer G, Passey R, Flournoy DJ, Blick K, Taylor Jr FB. Retrospective study comparing the pathophysiology of antibiotic treated and untreated Escherichia-coli-infused and Staphylococcus-aureus infused baboons. Circ Shock 1993; 41 (02) 88-102
    PubMedGoogle Scholar