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Thromb Haemost 1998; 80(05): 852-858
DOI: 10.1055/s-0037-1615370
Review Article
Schattauer GmbH

Adhesion of Leukocytes to Growing Arterial Thrombi

Inger Anne Hagberg
1   From Research Forum, Ullevaal University Hospital
,
Helge Einar Roald
2   From Department of Plastic Surgery, Rikshospitalet National Hospital, Oslo, Norway
,
Torstein Lyberg
1   From Research Forum, Ullevaal University Hospital
› Author Affiliations
Further Information

Publication History

Received 23 December 1997

Accepted after resubmission 04 August 1998

Publication Date:
07 December 2017 (online)

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Summary

Since the role of leukocytes found present in thrombi and haemo-static plugs is not clearly understood, we have investigated the interaction between leukocytes and growing thrombi in a human ex vivo model of arterial thrombogenesis. At a wall shear rate characteristic of moderately stenosed arteries (2600 s–1), granulocytes selectively accumulated at the luminal surface of platelet thrombi. The leukocyte adhesion seemed independent of fibrin formation and was clearly correlated to thrombus growth and platelet activation. In contrast, flow cytometry revealed that the expression of adhesion molecules (CD11a, CD11b, CD11c, CD3, CD14, CD62L, HLA-DR and binding of fibrinogen) on the surface of circulating leukocytes passing the thrombi was, on short term conditions (15 min), independent of thrombus growth. The adhered granulocytes probably play a pivotal role in limiting the size of the evolving thrombi, as suggested by our electron micrographs of the arterial thrombi showing lysed and phagocytosed platelets. Thus, granulocytes might play an active role in the acute/semiacute phase of local thromboregulation.

 

  • References

  • 1 Welch WH. The structure of the white thrombi. Trans Pathol Soc Phila 1887; 13: 281-300.
    PubMedGoogle Scholar
  • 2 Wester J, Sixma JJ, Geuze JJ, Heijnen HF. Morphology of the hemostatic plug in human skin wounds: transformation of the plug. Lab Invest 1979; 41: 182-92.
    PubMedGoogle Scholar
  • 3 Elstad MR, McIntyre TM, Prescott SM, Zimmerman GA. The interaction of leukocytes with platelets in blood coagulation. Current Opinion in Hematology 1995; 2: 47-54.
    CrossrefPubMedGoogle Scholar
  • 4 Marcus AJ, Safier LB. Thromboregulation: multicellular modulation of platelet reactivity in hemostasis and thrombosis. FASEB J 1993; 7: 516-22.
    CrossrefPubMedGoogle Scholar
  • 5 Kuijper PH, Gallardo Torres HI, van der Linden JA, Lammers JW, Sixma JJ, Koenderman L, Zwaginga JJ. Platelet-dependent primary hemostasis promotes selectin- and integrin-mediated neutrophil adhesion to damaged endothelium under flow conditions. Blood 1996; 87: 3271-81.
    PubMedGoogle Scholar
  • 6 Yeo EL, Sheppard JA, Feuerstein IA. Role of P-selectin and leukocyte activation in polymorphonuclear cell adhesion to surface adherent activated platelets under physiologic shear conditions (an injury vessel wall model). Blood 1994; 83: 2498-507.
    PubMedGoogle Scholar
  • 7 Sakariassen KS, Barstad RM. Mechanisms of thromboembolism at arterial plaques. Blood Coagul Fibrinolysis 1993; 4: 615-25.
    CrossrefPubMedGoogle Scholar
  • 8 Sakariassen KS, Aarts PA, de Groot PG, Houdijk WP, Sixma JJ. A perfusion chamber developed to investigate platelet interaction in flowing blood with human vessel wall cells, their extracellular matrix, and purified components. J Lab Clin Med 1983; 102: 522-35.
    PubMedGoogle Scholar
  • 9 Hagberg IA, Roald HE, Lyberg T. Platelet activation in flowing blood passing growing arterial thrombi. Arterioscler Thromb Vasc Biol 1997; 17: 1331-6.
    CrossrefPubMedGoogle Scholar
  • 10 Sakariassen KS, Joss R, Muggli R, Kuhn H, Tschopp TB, Sage H, Baumgartner HR. Collagen type III induced ex vivo thrombogenesis in humans. Role of platelets and leukocytes in deposition of fibrin. Arteriosclerosis 1990; 10: 276-84.
    CrossrefPubMedGoogle Scholar
  • 11 Roald HE, Orvim U, Bakken IJ, Barstad RM, Kierulf P, Sakariassen KS. Modulation of thrombotic responses in moderately stenosed arteries by cigarette smoking and aspirin ingestion. Arterioscler Thromb 1994; 14: 617-21.
    CrossrefPubMedGoogle Scholar
  • 12 Sakariassen KS, Weiss HJ, Baumgartner HR. Upstream thrombus growth impairs downstream thrombogenesis in non-anticoagulated blood: effect of procoagulant artery subendothelium and non-procoagulant collagen. Thromb Haemost 1991; 65: 596-600.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Sakariassen KS, Kuhn H, Muggli R, Baumgartner HR. Growth and stability of thrombi in flowing citrated blood: assessment of platelet-surface interactions with computer-assisted morphometry. Thromb Haemost 1988; 60: 392-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Hayat MA. Principles and Techniques of Electron Microscopy. The Macmillan Press Ltd; London: 1989. pp 264-5.
    Google Scholar
  • 15 Clevers H, Alarcon B, Wileman T, Terhorst C. The T cell receptor/CD3 complex: a dynamic protein ensemble. Annu Rev Immunol 1988; 6: 629-62.
    CrossrefPubMedGoogle Scholar
  • 16 Arnaout MA. Structure and function of the leukocyte adhesion molecules CD11/CD18. Blood 1990; 75: 1037-50.
    PubMedGoogle Scholar
  • 17 Viriyakosol S, Kirkland T. Knowledge of cellular receptors for bacterial endotoxin 1995. Clin Infect Dis 1995; 21 (Suppl. 02) S190-5.
    CrossrefPubMedGoogle Scholar
  • 18 Shimizu Y, Newman W, Tanaka Y, Shaw S. Lymphocyte interactions with endothelial cells. Immunol Today 1992; 13: 106-12.
    CrossrefPubMedGoogle Scholar
  • 19 Cheadle WG. The human leukocyte antigens and their relationship to infection. Am J Surg 1993; 165 Suppl. 75S-81S.
    CrossrefPubMedGoogle Scholar
  • 20 Kirchhofer D, Riederer MA, Baumgartner HR. Specific accumulation of circulating monocytes and polymorphonuclear leukocytes on platelet thrombi in a vascular injury model. Blood 1997; 89: 1270-8.
    PubMedGoogle Scholar
  • 21 Evangelista V, Manarini S, Rotondo S, Martelli N, Polischuk R, McGregor JL, de Gaetano G, Cerletti C. Platelet/polymorphonuclear leukocyte interaction in dynamic conditions: evidence of adhesion cascade and cross talk between P-selectin and the beta 2 integrin CD11b/CD18. Blood 1996; 88: 4183-94.
    PubMedGoogle Scholar
  • 22 Sheikh S, Nash GB. Continuous activation and deactivation of integrin CD11b/CD18 during de novo expression enables rolling neutrophils to immobilize on platelets. Blood 1996; 87: 5040-50.
    PubMedGoogle Scholar
  • 23 de Bruijne-Admiraal LG, Modderman PW, Von dem Borne AE, Sonnenberg A. P-selectin mediates Ca(2+)-dependent adhesion of activated platelets to many different types of leukocytes: detection by flow cytometry. Blood 1992; 80: 134-42.
    PubMedGoogle Scholar
  • 24 Smyth SS, Joneckis CC, Parise LV. Regulation of vascular integrins. Blood 1993; 81: 2827-43.
    PubMedGoogle Scholar
  • 25 Palabrica T, Lobb R, Furie BC, Aronovitz M, Benjamin C, Hsu YM, Sajer SA, Furie B. Leukocyte accumulation promoting fibrin deposition is mediated in vivo by P-selectin on adherent platelets. Nature 1992; 359: 848-51.
    CrossrefPubMedGoogle Scholar
  • 26 Spangenberg P. Adhesion of activated platelets to polymorphonuclear leukocytes. Thromb Res 1994; 74 (Suppl. 01) S35-44.
    CrossrefPubMedGoogle Scholar
  • 27 Bruehl RE, Moore KL, Lorant DE, Borregaard N, Zimmerman GA, McEver RP, Bainton DF. Leukocyte activation induces surface redistribution of P-selectin glycoprotein ligand-1. J Leukoc Biol 1997; 61: 489-99.
    CrossrefPubMedGoogle Scholar
  • 28 Zatta A, Pandolfo L, Caparrotta L, Prosdocimi M, Dejana E, Del Maschio A. Platelet aggregation induced by the endoperoxide analogue U46619 is inhibited by polymorphonuclear leukocyte ADPase activity. Arterioscler Thromb 1993; 13: 696-701.
    CrossrefPubMedGoogle Scholar
  • 29 Wright CD, Mulsch A, Busse R, Osswald H. Generation of nitric oxide by human neutrophils. Biochem Biophys Res Commun 1989; 160: 813-9.
    CrossrefPubMedGoogle Scholar
  • 30 Pidard D, Renesto P, Rabhi S, Chignard M. Regulation of the structure and activity of platelet adhesion receptors by leukocyte proteinases. Nouv Rev Fr Hematol 1994; 36 (Suppl. 01) S99-101.
    PubMedGoogle Scholar
  • 31 Lawrence MB, Springer TA. Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell 1991; 65: 859-73.
    CrossrefPubMedGoogle Scholar
  • 32 Su SB, Mukaida N, Matsushima K. Rapid secretion of intracellularly pre-stored interleukin-8 from rabbit platelets upon activation. J Leukoc Biol 1996; 59: 420-6.
    CrossrefPubMedGoogle Scholar
  • 33 Kishimoto TK, Jutila MA, Berg EL, Butcher EC. Neutrophil Mac-1 and MEL-14 adhesion proteins inversely regulated by chemotactic factors. Science 1989; 245: 1238-41.
    CrossrefPubMedGoogle Scholar
  • 34 Kähler H, Lyberg T. Anticoagulant selection influences the regulation of leukocyte adhesion molecules in LPS-stimulated human whole blood in vitro. 23rd World Congress of Medical Technology 28 June-3 July1998, Singapore (Abstract).
    PubMedGoogle Scholar
  • 35 Ruf A, Patscheke H. Platelet-induced neutrophil activation: platelet-expressed fibrinogen induces the oxidative burst in neutrophils by an interaction with CD11C/CD18. Br J Haematol 1995; 90: 791-6.
    CrossrefPubMedGoogle Scholar
  • 36 Neumann FJ, Marx N, Gawaz M, Brand K, Ott I, Rokitta C, Sticherling C, Meinl C, May A, Schomig A. Induction of cytokine expression in leukocytes by binding of thrombin-stimulated platelets. Circulation 1997; 95: 2387-94.
    CrossrefPubMedGoogle Scholar
  • 37 Osterud B. Cellular interactions in tissue factor expression by blood monocytes. Blood Coagul Fibrinolysis 1995; 6 (Suppl. 01) S20-5.
    PubMedGoogle Scholar