Modulation of the expression and activity of cyclooxygenases in normal and accelerated erythropoiesis

Bianca Rocca, Paola Secchiero, Claudio Celeghini, Franco O. Ranelletti, Giovanni Ciabattoni, Nicola Maggiano, Aida Habib, Bianca M. Ricerca, Elisa Barbarotto, Carlo Patrono, Giorgio Zauli

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Abstract

The present study was aimed at characterizing the expression and activity of cyclooxygenase (COX) isoenzymes in erythropoiesis. The expression and activity of cyclooxygenase (COX) and prostaglandin (PG) synthases were investigated in: 1) erythroblasts developed in culture from human CD34 + hematopoietic progenitors, 2) erythroblasts in bone marrow specimens, and 3) peripheral erythrocytes isolated from healthy donors and from patients with a high regeneration rate of erythrocytes. While COX-1 protein was observed at each stage of erythroblast development, COX-2 protein was induced at later stages through a p38/MAPK-dependent pathway. Both COX isoforms were also observed in mature erythroblasts of the bone marrow. Erythroblasts developed in culture synthesized significantly more PGE2 than TXB2 and indomethacin delayed erythroid maturation. COX-1 and COX-2 were also observed in erythrocytes by immunostainings, although COX expression was confined to a fraction of circulating erythrocytes. Peripheral erythrocytes synthesized low but detectable amounts of PGE2 and TXB2. Similarly to erythroblast progenitors, PGE2 was the prevalent prostanoid released by erythrocytes. This biosynthetic capacity was significantly increased in erythrocytes from patients with accelerated erythropoiesis as compared to controls. Both COX isoforms are present and enzymatically active during human erythropoiesis, although with different kinetics, and COX-derived prostanoids may play a role in erythroid maturation. Furthermore, peripheral erythrocytes retain in part the capacity of expressing COX and synthesizing prostanoids, which may contribute to the hemostatic/thrombotic response to vascular injury in different diseases, including congenital hemolytic disorders.

Original languageEnglish
Pages (from-to)925-934
Number of pages10
JournalExperimental Hematology
Volume32
Issue number10
DOIs
Publication statusPublished - Oct 2004

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ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

Rocca, B., Secchiero, P., Celeghini, C., Ranelletti, F. O., Ciabattoni, G., Maggiano, N., Habib, A., Ricerca, B. M., Barbarotto, E., Patrono, C., & Zauli, G. (2004). Modulation of the expression and activity of cyclooxygenases in normal and accelerated erythropoiesis. Experimental Hematology, 32(10), 925-934. https://doi.org/10.1016/j.exphem.2004.07.010