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

Bianca Rocca, Paola Secchiero, Giovanni Ciabattoni, Franco O. Ranelletti, Lucia Catani, Lia Guidotti, Elisabetta Melloni, Nicola Maggiano, Giorgio Zauli, Carlo Patrono

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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 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.

Original languageEnglish
Pages (from-to)7634-7639
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number11
Publication statusPublished - May 28 2002

ASJC Scopus subject areas

  • Genetics
  • General


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