Cyclooxygenase-2 expression is induced during human megakaryopoiesis and characterizes newly formed platelets

Bianca Rocca, Franco Oreste Ranelletti, Carlo Patrono, P Secchiero, G Ciabattoni, L Catani, L Guidotti, E Melloni, N Maggiano, G Zauli

Risultato della ricerca: Contributo in rivistaArticolo in rivista

292 Citazioni (Scopus)

Abstract

Cyclooxygenase (COX)-1 or -2 and prostaglandin (PG) synthases catalyze the formation of various PGs and thromboxane (TX) A(2). We have investigated the expression and activity of COX-1 and -2 during human megakaryocytopoiesis. We analyzed megakaryocytes from bone marrow biopsies and derived from thrombopoietin-treated CD34(+) hemopoietic progenitor cells in culture. Platelets were obtained from healthy donors and patients with high platelet regeneration because of immune thrombocytopenia or peripheral blood stem cell transplantation. By immunocytochemistry, COX-1 was observed in CD34(+) cells and in megakaryocytes at each stage of maturation, whereas COX-2 was induced after 6 days of culture, and remained detectable in mature megakaryocytes. CD34(+) cells synthesized more PGE(2) than TXB(2) (214 +/- 50 vs. 30 +/- 10 pg/10(6) cells), whereas the reverse was true in mature megakaryocytes (TXB(2) 8,440 +/- 2,500 vs. PGE(2) 906 +/- 161 pg/10(6) cells). By immunostaining, COX-2 was observed in <10% of circulating platelets from healthy controls, whereas up to 60% of COX-2-positive platelets were found in patients. A selective COX-2 inhibitor reduced platelet production of both PGE(2) and TXB(2) to a significantly greater extent in patients than in healthy subjects. Finally, we found that COX-2 and the inducible PGE-synthase were coexpressed in mature megakaryocytes and in platelets. We conclude that both COX-isoforms contribute to prostanoid formation during human megakaryocytopoiesis and that COX-2-derived PGE(2) and TXA(2) may play an unrecognized role in inflammatory and hemostatic responses in clinical syndromes associated with high platelet turnover.
Lingua originaleEnglish
pagine (da-a)7634-7639
Numero di pagine6
RivistaProceedings of the National Academy of Sciences of the United States of America
Volume99
DOI
Stato di pubblicazionePubblicato - 2002

Keywords

  • Antigens, CD
  • Antigens, CD34
  • Arachidonic Acid
  • Blood Platelets
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Hematopoiesis
  • Hematopoietic Stem Cells
  • Humans
  • Indomethacin
  • Isoenzymes
  • Megakaryocytes
  • Membrane Proteins
  • Phenotype
  • Prostaglandin-Endoperoxide Synthases
  • Thrombopoietin

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