PDF herunterladen
Thromb Haemost 1998; 80(01): 171-175
DOI: 10.1055/s-0037-1615158
Rapid Communication
Schattauer GmbH

Peripheral Blood Platelets Express VEGF-C and VEGF which Are Released during Platelet Activation

Ulla Wartiovaara
1   Departments of Clinical Chemistry and Biomedicine
,
Petri Salven
,
Hanna Mikkola
1   Departments of Clinical Chemistry and Biomedicine
,
Riitta Lassila
3   Wihuri Research Institute, Helsinki, Finland
,
Jaakko Kaukonen
1   Departments of Clinical Chemistry and Biomedicine
,
Vladimir Joukov
4   Molecular/Cancer Biology Laboratory, Haartman Institute, University of Helsinki, Helsinki University, Finland
,
Arto Orpana
1   Departments of Clinical Chemistry and Biomedicine
,
Ari Ristimäki
6   Obstetr. Gynecol, University of Helsinki, Helsinki, Finland
,
Markku Heikinheimo
,
Heikki Joensuu
,
Kari Alitalo
4   Molecular/Cancer Biology Laboratory, Haartman Institute, University of Helsinki, Helsinki University, Finland
,
Aarno Palotie
1   Departments of Clinical Chemistry and Biomedicine
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received 18. August 1997

Accepted after resubmission 30. März 1998

Publikationsdatum:
08. Dezember 2017 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Summary

VEGF-C is a recently characterised endothelial growth factor structurally related to vascular endothelial growth factor (VEGF). We studied the expression of VEGF-C and VEGF in the cells of peripheral blood and in the umbilical cord blood CD 34+ cells, representing haematopoietic progenitor cells. Expression of VEGF-C was detected in the CD34+ cells. In peripheral blood VEGF-C mRNA was restricted to platelets and T-cells. In contrast to the expression pattern of VEGF-C, VEGF mRNA was detected in all peripheral blood cell fractions studied, and also in CD34+ cells. VEGF-C mRNA was also detected in fresh bone marrow samples of acute leukaemia patients, but the expression did not show lineage specificity. VEGF-C and VEGF polypeptides were present in platelets and they were released from activated platelets together with the release of β-thromboglobulin, suggesting that VEGF-C and VEGF reside in the α-granules of platelets. VEGF-C and VEGF, released from activated platelets, may have a role in angiogenesis during wound healing, and possibly also in other pathological conditions, such as atherosclerosis, tumour growth, and metastasis formation.

 

  • References

  • 1 Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nature Med 1995; 1: 27-31.
    CrossrefPubMedGoogle Scholar
  • 2 Clauss M, Gerlach M, Gerlach H, Brett J, Wang F, Familletti PC, Pan YC, Olander JV, Connolly DT, Stern D. Vascular permeability factor: a tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration. J Exp Med 1990; 172: 1535-45.
    CrossrefPubMedGoogle Scholar
  • 3 Dvorak HF, Brown LF, Detmar M, Dvorak AM. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 1995; 146: 1029-39.
    PubMedGoogle Scholar
  • 4 de Vries C, Escobedo JA, Ueno H, Houck K, Ferrara N, Williams LT. The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science 1992; 255: 989-91.
    CrossrefPubMedGoogle Scholar
  • 5 Terman BI, Dougher VM, Carrion ME, Dimitrov D, Armellino DC, Gospodarowicz D, Bohlen P. Identification of the KDR tyrosine kinase as a receptor for vascular endothelial cell growth factor. Biochem Biophys Res Commun 1992; 187: 1579-86.
    CrossrefPubMedGoogle Scholar
  • 6 Mustonen T, Alitalo K. Endothelial receptor tyrosine kinases involved in angiogenesis. J Cell Biol 1995; 129: 895-8.
    CrossrefPubMedGoogle Scholar
  • 7 Clauss M, Weich H, Breier G, Knies U, Rockl W, Waltenberger J, Risau W. The vascular endothelial growth factor receptor Flt-1 mediates biological activities. Implications for a functional role of placenta growth factor in monocyte activation and chemotaxis. J Biol Chem 1996; 271: 17629-34.
    CrossrefPubMedGoogle Scholar
  • 8 Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, Fahrig M, Vandenhoeck A, Harpal K, Eberhardt C, Declercq C, Pawling J, Moons L, Collen D, Risau W, Nagy A. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature 1996; 380: 435-9.
    CrossrefPubMedGoogle Scholar
  • 9 Ferrara N, Carver Moore K, Chen H, Dowd M, Lu L, O’Shea KS, Powell Braxton L, Hillan KJ, Moore MW. Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene. Nature 1996; 380: 439-42.
    CrossrefPubMedGoogle Scholar
  • 10 Fong GH, Rossant J, Gertsenstein M, Breitman ML. Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 1995; 376: 66-70.
    CrossrefPubMedGoogle Scholar
  • 11 Shalaby F, Rossant J, Yamaguchi TP, Gertsenstein M, Wu XF, Breitman ML, Schuh AC. Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 1995; 376: 62-6.
    CrossrefPubMedGoogle Scholar
  • 12 Olofsson B, Pajusola K, Kaipainen A, von Euler G, Joukov V, Saksela O, Orpana A, Pettersson RF, Alitalo K, Eriksson U. Vascular endothelial growth factor B, a novel growth factor for endothelial cells. Proc Natl Acad Sci USA 1996; 93: 2576-81.
    CrossrefPubMedGoogle Scholar
  • 13 Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E, Saksela O, Kalkkinen N, Alitalo K. A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO J 1996; 15: 290-8.
    PubMedGoogle Scholar
  • 14 Yamada Y, Nezu J, Shimane M Y. H. Molecular cloning of a novel vascular endothelial growth factor, VEGF-D. Genomics 1997; 42: 483-8.
    CrossrefPubMedGoogle Scholar
  • 15 Salven P, Lymboussaki A, Heikkilä P, Enholm B, Jääskelä-Saari H, Aase K, von Euler G, Eriksson U, Alitalo K, Joensuu H. Vascular endothelial growth factors VEGF-B and VEGF-C are expressed in human tumors. Am J Pathol. in press.
    PubMedGoogle Scholar
  • 16 Syrjälä MT. Labelling of granulocytes with radioindium: cell isolation and labelling parameters. Scand J Haem 1985; 35: 579-83.
    PubMedGoogle Scholar
  • 17 Milteneyi S, Guth S, Radbruch A, Pfluger E, Thiel A. Isolation of CD34+ Hematopoietic Progenitor Cells by High-Gradient Magnetic Cell Sorting (MACS). In: Hematopoietic stem cells. The Mulhouse Manual 1994. AlphaMed Press; Dayton: 1994: 201-13.
    Google Scholar
  • 18 Siljander P, Carpen O, Lassila R. Platelet-derived microparticles associate with fibrin during thrombosis. Blood 1996; 87: 4651-63.
    PubMedGoogle Scholar
  • 19 Teitel JM, Bauer KA, Lau HK, Rosenberg RD. Studies of the prothrombin activation pathway utilizing radioimmunoassays for the F2/F1 + 2 fragment and thrombin-antithrombin complex. Blood 1982; 59: 1086-97.
    PubMedGoogle Scholar
  • 20 Yamamura M, Uyemura K, Deans RJ, Weinberg K, Rea TH, Bloom BR, Modlin RL. Defining protective responses to pathogens: cytokine profiles in lepropsy lesions. Science 1991; 254: 277-9.
    CrossrefPubMedGoogle Scholar
  • 21 Ikonen E, Manninen T, Peltonen L, Syvänen AC. Quantitative determina tion of rare mRNA species by PCR and solid-phase minisequencing. PCR Methods & Applications 1992; 1: 234-40.
    PubMedGoogle Scholar
  • 22 Armstrong E, Kastury K, Aprelikova O, Bullrich F, Nezelof C, Gogusev J, Wasmuth JJ, Alitalo K, Morris S, Huebner K. FLT4 receptor tyrosine kinase gene mapping to chromosome band 5q35 in relation to the t(2;5), t(5;6), and t(3;5) translocations. Genes, Chromosomes & Cancer 1993; 7: 144-51.
    CrossrefPubMedGoogle Scholar
  • 23 Joukov V, Sorsa T, Kumar V, Jeltsch M, Claesson-Welsh L, Cao Y, Saksela O, Kalkkinen N, Alitalo K. Proteolytic processing regulates receptor specifity and activity of VEGF-C. EMBO J 1997; 16: 3898-911.
    CrossrefPubMedGoogle Scholar
  • 24 Paunio T, Kangas H, Kalkkinen N, Haltia M, Palo J, Peltonen L. Toward understanding the pathogenic mechanisms in gelsolin-related amyloidosis: in vitro expression reveals an abnormal gelsolin fragment. Hum Mol Gen 1994; 3: 2223-9.
    CrossrefPubMedGoogle Scholar
  • 25 Salven P, Teerenhovi L, Joensuu H. A high pretreatment serum vascular endothelial growth factor concentration is associated with poor outcome in non-Hodgkin’s lymphoma. Blood 1997; 90: 3167-72.
    CrossrefPubMedGoogle Scholar
  • 26 Kennedy M, Firpo M, Choi K, Wall C, Robertson S, Kabrun N, Keller G. A common precursor for primitive erythropoiesis and definitive haematopoiesis. Nature 1997; 386: 488-93.
    CrossrefPubMedGoogle Scholar
  • 27 Fiedler W, Graeven U, Ergün S, Verago S, Kilic N, Stockschläder M, Hoss feld DK. Vascular endothelial growth factor, a possible paracrine in human acute myeloid leukemias. Blood 1997; 89: 1870-5.
    PubMedGoogle Scholar
  • 28 Jones CL. Response of a human megakaryotic cell line to thrombin: increase in intracellular free calcium and mitogen release. Biochim Biophys Acta 1992; 1136: 272-82.
    CrossrefPubMedGoogle Scholar
  • 29 Ross R. Platelet-derived growth factor. Lancet 1989; 1: 1179-82.
    PubMedGoogle Scholar
  • 30 Möhle R, Green D, Moore MA, Nachman RL, Rafii S. Constitutive produc tion and thrombin-induced release of vascular endothelial growth factor by human megakaryocytes and platelets. Proc Natl Acad Sci USA 1997; 94: 663-8.
    CrossrefPubMedGoogle Scholar
  • 31 Harrison P, Wilbourn B, Debili N, Vainchenker W, Breton Gorius J, Lawrie AS, Masse JM, Savidge GF, Cramer EM. Uptake of plasma fibrinogen into the alpha granules of human megakaryocytes and platelets. J Clin Invest 1989; 84: 1320-4.
    CrossrefPubMedGoogle Scholar
  • 32 Brown LF, Yeo KT, Berse B, Yeo TK, Senger DR, Dvorak HF, van de Water L. Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing. J Exp Med 1992; 176: 1375-9.
    CrossrefPubMedGoogle Scholar
  • 33 Detmar M, Yeo KT, Nagy JA, van de Water L, Brown LF, Berse B, Elicker BM, Ledbetter S, Dvorak HF. Keratinocyte-derived vascular permeability factor (vascular endothelial growth factor) is a potent mitogen for dermal microvascular endothelial cells. J Invest Dermatol 1995; 105: 44-50.
    CrossrefPubMedGoogle Scholar
  • 34 Beitz JG, Kim I, Calabresi P, Frackelton ARJ. Human microvascular endothelial cells express receptors for platelet-derived growth factor. Proc Natl Acad Sci USA 1991; 88: 2021-5.
    CrossrefPubMedGoogle Scholar
  • 35 Kuzuya M, Satake S, Esaki T, Yamada K, Hayashi T, Naito M, Asai K, Iguchi A. Induction of angiogenesis by smooth muscle cell-derived factor: possible role in neovascularization in atherosclerotic plaque. J Cellular Physiol 1995; 164: 658-67.
    CrossrefPubMedGoogle Scholar