Download PDF
Thromb Haemost 2006; 96(04): 498-504
DOI: 10.1160/TH06-05-0250
Platelets and Blood Cells
Schattauer GmbH

Potential role of activated platelets in homing of human endothelial progenitor cells to subendothelial matrix

Eli I. Lev
1   The Methodist Hospital Research Institute and The Methodist DeBakey Heart Center, Houston, Texas, USA
,
Zeev Estrov
2   The Methodist Hospital, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
,
Khatira Aboulfatova
3   Thrombosis Research Section, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
,
David Harris
2   The Methodist Hospital, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
,
Juan F. Granada
1   The Methodist Hospital Research Institute and The Methodist DeBakey Heart Center, Houston, Texas, USA
,
Carlos Alviar
1   The Methodist Hospital Research Institute and The Methodist DeBakey Heart Center, Houston, Texas, USA
,
Neal S. Kleiman
1   The Methodist Hospital Research Institute and The Methodist DeBakey Heart Center, Houston, Texas, USA
,
Jing-fei Dong
3   Thrombosis Research Section, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
› Author Affiliations
Further Information

Publication History

Received 08 May 2006

Accepted after resubmission 31 July 2006

Publication Date:
29 November 2017 (online)

Also available at
    Permissions and Reprints

Summary

Endothelial progenitor cells (EPCs) mobilize from the bone marrow in response to tissue injury and participate in vascular repair. However, there is limited data about the homing mechanisms of EPCs to vascular injury sites. Recently animal experiments indicated that platelets playa role in recruitment of EPCs to injury sites. However, data on the possible interaction between platelets and EPCs within the human system are limited. We, therefore, examined in-vitro human platelet-EPC interaction under static and flow conditions. Human EPCs were isolated from donated buffy coats by magnetic microbeads and flow cytometry cell sorting using CD133 and VEGFR-2, respectively, as markers. Platelets were tested in the form of washed platelets, platelet rich plasma or whole blood. EPCs formed heterotypic aggregates with resting platelets under static conditions, an interaction that was greatly enhanced when platelets were activated by collagen, ADP or thrombin-activation peptide. The platelet-EPC interaction was inhibited by antibodies to P-selectin or P-selectin glycoprotein ligand-1 (PSGL-1), but not by antibodies to glycoproteins Ib-IX-V or IIb/IIIa. When perfused over activated platelets under shear stress of 2.5 dyn/cm2, EPCs tethered to platelayers and either adhered immediately or rolled a short distance before adhering. In addition, platelets promoted the colonization of adherent EPCs in culture conditions. Consistent with recent animal studies, these findings demonstrate that human EPCs interact in vitro with activated platelets under static and flow conditions, mediated through P-selectin–PSGL-1 interaction. This interaction may be a central mechanism for homing of EPCs to vascular injury sites.

Keywords

Platelets - endothelial progenitor cells - interaction
 

  • References

  • 1 Asahara T, Murohara T, Sullivan A. et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997; 275: 964-67.
    CrossrefPubMedGoogle Scholar
  • 2 Lin Y, Weisdorf DJ, Solovey A. et al. Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest 2000; 105: 71-7.
    CrossrefPubMedGoogle Scholar
  • 3 Peichev M, Naiyer AJ, Pereira D. et al. Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifiesa population of functional endothelial precursors. Blood 2000; 95: 952-8.
    PubMedGoogle Scholar
  • 4 Hristov M, Weber C. Endothelial progenitor cells: characterization, pathophysiology, and possible clinical relevance. J Cell Mol Med 2004; 08: 498-508.
    CrossrefPubMedGoogle Scholar
  • 5 Asahara T, Masuda H, Takahashi T. et al. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ Res 1999; 85: 221-8.
    CrossrefPubMedGoogle Scholar
  • 6 Gehling UM, Ergun S, Schumacher U. et al. In vitro differentiation of endothelial cells from AC133-positive progenitor cells. Blood 2000; 95: 3106-12.
    PubMedGoogle Scholar
  • 7 Dimmeler S, Zeiher AM. Vascular repair by circulating endothelial progenitor cells: the missing link in atherosclerosis?. J Mol Med 2004; 82: 671-7.
    CrossrefPubMedGoogle Scholar
  • 8 Walter DH, Rittig K, Bahlmann FH. et al. Statin therapy accelerates reendothelialization: a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells. Circulation 2002; 105: 3017-24.
    CrossrefPubMedGoogle Scholar
  • 9 Werner N, Priller J, Laufs U. et al. Bone marrow-derived progenitor cells modulate vascular reendothelialization and neointimal formation: effect of 3-hydroxy3-methylglutaryl coenzymea reductase inhibition. Arterioscler Thromb Vasc Biol 2002; 22: 1567-72.
    CrossrefPubMedGoogle Scholar
  • 10 Griese DP, Ehsan A, Melo LG. et al. Isolation and transplantation of autologous circulating endothelial cells into denuded vessels and prosthetic grafts: implications for cell-based vascular therapy. Circulation 2003; 108: 2710-5.
    CrossrefPubMedGoogle Scholar
  • 11 Gill M, Dias S, Hattori K. et al. Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+) endothelial precursor cells. Circ Res 2001; 88: 167-74.
    CrossrefPubMedGoogle Scholar
  • 12 Lev EI, Kleiman NS, Birnbaum Y. et al. Circulating endothelial progenitor cells and coronary collaterals in patients with non-ST segment elevation myocardial infarction. J Vasc Res 2005; 42: 408-14.
    CrossrefPubMedGoogle Scholar
  • 13 Janowska-Wieczorek A, Majka M, Kijowski J. et al. Platelet-derived microparticles bind to hematopoietic stem/progenitor cells and enhance their engraftment. Blood 2001; 98: 3143-9.
    CrossrefPubMedGoogle Scholar
  • 14 Hidalgo A, Weiss LA, Frenette PS. Functional selectin ligands mediating human CD34(+) cell interactions with bone marrow endothelium are enhanced postnatally. J Clin Invest 2002; 110: 559-69.
    CrossrefPubMedGoogle Scholar
  • 15 Vajkoczy P, Blum S, Lamparter M, Mailhammer R. et al. Multistep nature of microvascular recruitment of ex vivo-expanded embryonic endothelial progenitor cells during tumor angiogenesis. J Exp Med 2003; 197: 1755-65.
    CrossrefPubMedGoogle Scholar
  • 16 Pintucci G, Froum S, Pinnell J. et al. Trophic effects of platelets on cultured endothelial cells are mediated by platelet-associated fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF). Thromb Haemost 2002; 88: 834-42.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Langer H, May AE, Daub K. et al. Adherent platelets recruit and induce differentiation of murine embryonic endothelial progenitor cells to mature endothelial cells in vitro . Circ Res 2006; 98: 289.
    PubMedGoogle Scholar
  • 18 Massberg S, Konrad I, Schurzinger K. et al. Platelets secrete stromal cell-derived factor 1alpha and recruit bone marrow-derived progenitor cells to arterial thrombi in vivo. J Exp Med 2006; 203: 1221-33.
    CrossrefPubMedGoogle Scholar
  • 19 de Boer HC, Verseyden C, Ulfman LH. et al. Fibrin and activated platelets cooperatively guide stem cells to a vascular injury and promote differentiation towards an endothelial cell phenotype. Arterioscler Thromb Vasc Biol 2006; 26: 1653-9.
    CrossrefPubMedGoogle Scholar
  • 20 Urbich C, Dimmeler S. Endothelial progenitor cells: characterization and role in vascular biology. Circ Res 2004; 95: 343-53.
    CrossrefPubMedGoogle Scholar
  • 21 Nowak G, Karrar A, Holmen C. et al. Expression of vascular endothelial growth factor receptor-2 or Tie-2 on peripheral blood cells defines functionally competent cell populations capable of reendothelialization. Circulation 2004; 110: 3699-707.
    CrossrefPubMedGoogle Scholar
  • 22 Fredrickson BJ, Dong JF, McIntire LV. et al. Sheardependent rolling on von Willebrand factor of mammalian cells expressing the platelet glycoprotein- IX-V complex. Blood. 198 92. 3684-3.
    PubMedGoogle Scholar
  • 23 Dong JF, Berndt MC, Schade A. et al. Ristocetindependent, but not botrocetin-dependent, binding of von Willebrand factor to the platelet glycoprotein Ib- IX-V complex correlates with shear-dependent interactions. Blood 2001; 97: 162-8.
    CrossrefPubMedGoogle Scholar
  • 24 Snapp KR, Ding H, Atkins K. et al. A novel P-selectin glycoprotein ligand-1 monoclonal antibody recognizes an epitope within the tyrosine sulfate motif of human PSGL-1 and blocks recognition of both P- and L-selectin. Blood 1998; 91: 154-64.
    PubMedGoogle Scholar
  • 25 Moser M, Bertram U, Peter K. et al. Abciximab, eptifibatide, and tirofiban exhibit dose-dependent potencies to dissolve platelet aggregates. J Cardiovasc Pharmacol 2003; 41: 586-92.
    CrossrefPubMedGoogle Scholar
  • 26 Schade AJ, Arya M, Gao S. et al. Cytoplasmic truncation of glycoprotein ibalpha weakens its interaction with von Willebrand factor and impairs cell adhesion. Biochemistry 2003; 42: 2245-51.
    CrossrefPubMedGoogle Scholar
  • 27 Lawrence MB, McIntire LV, Eskin SG. Effect of flow on polymorphonuclear leukocyte/endothelial cell adhesion. Blood 1987; 70: 1284-90.
    PubMedGoogle Scholar
  • 28 Hill JM, Zalos G, Halcox JP. et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 2003; 348: 593-600.
    CrossrefPubMedGoogle Scholar
  • 29 Mazo IB, Gutierrez-Ramos JC, Frenette PS. et al. Hematopoietic progenitor cell rolling in bone marrow microvessels: parallel contributions by endothelial selectins and vascular cell adhesion molecule 1. J Exp Med 1998; 188: 465-74.
    CrossrefPubMedGoogle Scholar
  • 30 Wagner DD. New links between inflammation and thrombosis. Arterioscler Thromb Vasc Biol 2005; 25: 1321-4.
    CrossrefPubMedGoogle Scholar
  • 31 Quirici N, Soligo D, Caneva L. et al. Differentiation and expansion of endothelial cells from human bone marrow CD133(+) cells. Br J Haematol 2001; 115: 186-94.
    CrossrefPubMedGoogle Scholar
  • 32 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
  • 33 Buttrum SM, Hatton R, Nash GB. Selectin-mediated rolling of neutrophils on immobilized platelets. Blood 1993; 82: 1165-74.
    PubMedGoogle Scholar
  • 34 Moore KL, Patel KD, Bruehl RE. et al. P-selectin glycoprotein ligand-1 mediates rolling of human neutrophils on P-selectin. J Cell Biol 1995; 128: 661-71.
    CrossrefPubMedGoogle Scholar
  • 35 Alon R, Rossiter H, Wang X. et al. Distinct cell surface ligands mediate T lymphocyte attachment and rolling on P and E selectin under physiological flow. J Cell Biol 1994; 127: 1485-95.
    CrossrefPubMedGoogle Scholar
  • 36 Kuijper PH, Gallardo HITorres, Houben LA. et al. P-selectin and MAC-1 mediate monocyte rolling and adhesion to ECM-bound platelets under flow conditions. J Leukoc Biol 1998; 64: 467-73.
    CrossrefPubMedGoogle Scholar
  • 37 Weber C, Springer TA. Neutrophil accumulation on activated, surface-adherent platelets in flow is mediated by interaction of Mac-1 with fibrinogen bound to alphaIIbbeta3 and stimulated by platelet-activating factor. J Clin Invest 1997; 100: 2085-93.
    CrossrefPubMedGoogle Scholar
  • 38 Zernecke A, Schober A, Bot I. et al. SDF-1alpha/ CXCR4 axis is instrumental in neointimal hyperplasia and recruitment of smooth muscle progenitor cells. Circ Res 2005; 96: 784-91.
    CrossrefPubMedGoogle Scholar
  • 39 Pihusch V, Pihusch M, Penovici M. et al. Transforming growth factor beta-1 released from platelets contributes to hypercoagulability in veno-occlusive disease following hematopoetic stem cell transplantation. Thromb Res 2005; 116: 233-40.
    CrossrefPubMedGoogle Scholar
  • 40 Zhu C, Ying D, Zhou D. et al. Expression of TGFbeta1 in smooth muscle cells regulates endothelial progenitor cells migration and differentiation. J Surg Res 2005; 125: 151-6.
    CrossrefPubMedGoogle Scholar
  • 41 Dimmeler S. Platelet-derived growth factor CC--a clinically useful angiogenic factor at last?. N Engl J Med 2005; 352: 1815-6.
    CrossrefPubMedGoogle Scholar
  • 42 Vasa M, Fichtlscherer S, Adler K. et al. Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease. Circulation 2001; 103: 2885-90.
    CrossrefPubMedGoogle Scholar
  • 43 Sanguigni V, Pignatelli P, Lenti L, Ferro D. et al. Short-term treatment with atorvastatin reduces platelet CD40 ligand and thrombin generation in hypercholesterolemic patients. Circulation 2005; 111: 412-9.
    CrossrefPubMedGoogle Scholar
  • 44 Watala C. Blood platelet reactivity and its pharmacological modulation in (people with) diabetes mellitus. Curr Pharm Des 2005; 11: 2331-65.
    CrossrefPubMedGoogle Scholar