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Thromb Haemost 2010; 104(06): 1184-1192
DOI: 10.1160/TH10-05-0308
Platelets and Blood Cells
Schattauer GmbH

Platelets enhance lymphocyte adhesion and infiltration into arterial thrombus

Hu Hu
1   Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China
,
Linjing Zhu
1   Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China
2   Karolinska Institute, Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital (Solna), Stockholm, Sweden
,
Zhangsen Huang
1   Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China
,
Qiushang Ji
3   Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China
,
Madhumita Chatterjee
2   Karolinska Institute, Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital (Solna), Stockholm, Sweden
,
Wei Zhang
2   Karolinska Institute, Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital (Solna), Stockholm, Sweden
,
Nailin Li
1   Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China
2   Karolinska Institute, Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital (Solna), Stockholm, Sweden
› Institutsangaben Financial support:This work was supported by grants from the Swedish Research Council, the Swedish Heart-Lung Foundation, the National Natural Science Foundation of China (30700267), the Natural Science Foundation of Zhejiang Province (Y206095), the Karolinska Institute, the Swedish Society of Medicine, and the Stockholm County Council.
Weitere Informationen

Publikationsverlauf

Received: 20. Mai 2010

Accepted after major revision: 02. August 2010

Publikationsdatum:
24. November 2017 (online)

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Summary

Lymphocytes are present in atherosclerotic lesion. We hypothesise that platelets may facilitate lymphocyte infiltration into the arterial wall. Reconstituted human blood or whole blood was perfused through a collagen-coated parallel-plate flow chamber at different shear rates. Adhered platelets markedly enhanced lymphocyte adhesion that increased lymphocyte deposition from 10 ± 3 cells/mm2 of platelet-depleted blood to 38 ± 11 cells/mm2 of platelet-containing blood at the arterial shear rate of 500 s-1. Platelet-dependent lymphocyte adhesion was inhibited by P-selectin, CD40L, and GPIIb/IIIa-blocking agents, suggesting the involvement of multiple adhesion molecules in this heterotypic interaction. Lymphocyte deposition was more marked among T cells, and seen in both small and large cells. B and natural killer cell adhesion was, however, mainly seen in small cells. Platelet-conjugation facilitated lymphocyte adhesion, as suggested by the selective deposition of platelet-conjugated lymphocytes. In a mouse model of arterial thrombosis, FeCl3-induced thrombus formation markedly enhanced lymphocyte adhesion and infiltration into platelet thrombi, which was abolished by GPIIb/IIIa inhibition. In conclusion, platelets support lymphocyte adhesion under arterial flow conditions, which is selective among T cells and involves multiple adhesion molecules. Our data imply that platelets may facilitate the recruitment of circulating lymphocytes at the arterial injured sites.

Keywords

Platelets - lymphocytes - platelet-lymphocyte conjugates - arterial flow - thrombosis
 

  • References

  • 1 Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005; 352: 1685-1695.
    CrossrefPubMedGoogle Scholar
  • 2 Weber C. Platelets and chemokines in atherosclerosis: partners in crime. Circ Res 2005; 96: 612-616.
    CrossrefPubMedGoogle Scholar
  • 3 Davi G, Patrono C. Platelet activation and atherothrombosis. N Engl J Med 2007; 357: 2482-2494.
    CrossrefPubMedGoogle Scholar
  • 4 Langer HF, Gawaz M. Platelet-vessel wall interactions in atherosclerotic disease. Thromb Haemost 2008; 99: 480-486.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 5 Jennings LK. Mechanisms of platelet activation: need for new strategies to protect against platelet-mediated atherothrombosis. Thromb Haemost 2009; 102: 248-257.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 6 Muhlestein JB. Effect of antiplatelet therapy on inflammatory markers in atherothrombotic patients. Thromb Haemost 2010; 103: 71-82.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 7 Zhou X, Nicoletti A, Elhage R. et al. Transfer of CD4(+) T cells aggravates athero-sclerosis in immunodeficient apolipoprotein E knockout mice. Circulation 2000; 102: 2919-2922.
    CrossrefPubMedGoogle Scholar
  • 8 Caligiuri G, Nicoletti A, Poirier B. et al. Protective immunity against atherosclerosis carried by B cells of hypercholesterolemic mice. J Clin Invest 2002; 109: 745-753.
    CrossrefPubMedGoogle Scholar
  • 9 Ait-Oufella H, Salomon BL, Potteaux S. et al. Natural regulatory T cells control the development of atherosclerosis in mice. Nat Med 2006; 12: 178-180.
    CrossrefPubMedGoogle Scholar
  • 10 Huo Y, Schober A, Forlow SB. et al. Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E. Nat Med 2003; 9: 61-67.
    CrossrefPubMedGoogle Scholar
  • 11 Massberg S, Brand K, Gruner S. et al. A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation. J Exp Med 2002; 196: 887-896.
    CrossrefPubMedGoogle Scholar
  • 12 Koenen RR, von Hundelshausen P, Nesmelova IV. et al. Disrupting functional interactions between platelet chemokines inhibits atherosclerosis in hyperlipidemic mice. Nat Med 2009; 15: 97-103.
    CrossrefPubMedGoogle Scholar
  • 13 Li N. Platelet lymphocyte cross-talk. J Leukoc Biol 2008; 83: 1069-1078.
    CrossrefPubMedGoogle Scholar
  • 14 Lalor P, Nash GB. Adhesion of flowing leucocytes to immobilized platelets. Br J Haematol 1995; 89: 725-732.
    PubMedGoogle Scholar
  • 15 Pitchford SC, Momi S, Giannini S. et al. Platelet P-selectin is required for pulmonary eosinophil and lymphocyte recruitment in a murine model of allergic inflammation. Blood 2005; 105: 2074-2081.
    CrossrefPubMedGoogle Scholar
  • 16 Rinder HM, Bonan JL, Rinder CS. et al. Dynamics of leukocyte-platelet adhesion in whole blood. Blood 1991; 78: 1730-1737.
    PubMedGoogle Scholar
  • 17 Li N, Ji Q, Hjemdahl P. Platelet-lymphocyte conjugation differs between lymphocyte subpopulations. J Thromb Haemost 2006; 4: 874-881.
    CrossrefPubMedGoogle Scholar
  • 18 Li N, Goodall AH, Hjemdahl P. Efficient flow cytometric assay for platelet-leukocyte aggregates in whole blood using fluorescence signal triggering. Cytometry 1999; 35: 154-161.
    CrossrefPubMedGoogle Scholar
  • 19 Diacovo TG, Puri KD, Warnock RA. et al. Platelet-mediated lymphocyte delivery to high endothelial venules. Science 1996; 273: 252-255.
    CrossrefPubMedGoogle Scholar
  • 20 Elzey BD, Tian J, Jensen RJ. et al. Platelet-mediated modulation of adaptive immunity. A communication link between innate and adaptive immune compartments. Immunity 2003; 19: 9-19.
    CrossrefPubMedGoogle Scholar
  • 21 Gregg EO, Yarwood L, Wagstaffe MJ. et al. Immunomodulatory properties of platelet factor 4: prevention of concanavalin A suppressor-induction in vitro and augmentation of an antigen-specific delayed-type hypersensitivity response in vivo. Immunology 1990; 70: 230-234.
    PubMedGoogle Scholar
  • 22 Liu CY, Battaglia M, Lee SH. et al. Platelet factor 4 differentially modulates CD4+CD25+ (regulatory) versus CD4+CD25– (nonregulatory) T cells. J Immunol 2005; 174: 2680-2686.
    CrossrefPubMedGoogle Scholar
  • 23 Hansson GK, Libby P, Schonbeck U. et al. Innate and adaptive immunity in the pathogenesis of atherosclerosis. Circ Res 2002; 91: 281-291.
    CrossrefPubMedGoogle Scholar
  • 24 Theilmeier G, Michiels C, Spaepen E. et al. Endothelial von Willebrand factor recruits platelets to atherosclerosis- prone sites in response to hypercholesterolemia. Blood 2002; 99: 4486-4493.
    CrossrefPubMedGoogle Scholar
  • 25 Hu H, Varon D, Hjemdahl P. et al. Platelet-leukocyte aggregation under shear stress: differential involvement of selectins and integrins. Thromb Haemost 2003; 90: 679-687.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 26 Denis C, Methia N, Frenette PS. et al. A mouse model of severe von Willebrand disease: defects in hemostasis and thrombosis. Proc Natl Acad Sci USA 1998; 95: 9524-9529.
    CrossrefPubMedGoogle Scholar
  • 27 van Gils JM, da Costa Martins PA, Mol A. et al. Transendothelial migration drives dissociation of platelet-monocyte complexes. Thromb Haemost 2008; 100: 271-279.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 28 Shantsila E, Lip GY. The role of monocytes in thrombotic disorders. Insights from tissue factor, monocyte-platelet aggregates and novel mechanisms. Thromb Haemost 2009; 102: 916-924.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 29 Ruggeri ZM. Old concepts and new developments in the study of platelet aggregation. J Clin Invest 2000; 105: 699-701.
    CrossrefPubMedGoogle Scholar