Inhibition of tissue factor expression by hydroxyurea in polymorphonuclear leukocytes from patients with myeloproliferative disorders: A new effect for an old drug?

Norma Maugeri, G. Giordano, M. P. Petrilli, V. Fraticelli, G. De Gaetano, C. Cerletti, S. Storti, M. B. Donati

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Polymorphonuclear leukocytes (PMN) from healthy subjects can produce and store tissue factor (TF), which is expressed on PMN surface upon in vitro stimulation with P-selectin. Results: We report here that platelets and PMN from 12 patients with myeloproliferative disorders (MPD) (six with polycythemia vera, six with essential thrombocythemia) show up regulation of P-selectin and TF, respectively, in the absence of any in vitro challenge. The number of circulating mixed platelet-PMN aggregates was also increased. PMN TF expression as well as mixed platelet-PMN aggregates, but not platelet P-selectin, were significantly reduced in six MPD patients after treatment with hydroxyurea (HU). In vitro studies performed on PMN separated from healthy donors confirmed HU effects (0-1400 μM). HU prevented both P-selectin-induced TF expression and mixed cell aggregate formation. The inhibitory effect of HU was specific for P-selectin-induced PMN activation, as it did not affect formyl-methionyl-leucyl-phenylalanine-induced PMN TF expression. Conclusions: In MPD patients, platelet P-selectin-mediated TF expression on circulating PMN may play a role in thrombus formation and represents a novel target for the antithrombotic activity of HU.

Original languageEnglish
Pages (from-to)2593-2598
Number of pages6
JournalJournal of Thrombosis and Haemostasis
Volume4
Issue number12
DOIs
Publication statusPublished - Dec 2006

Keywords

  • Hydroxyurea
  • Myeloproliferative disorders
  • P-selectin
  • Platelet-leukocyte aggregates
  • Polymorphonuclear leukocytes
  • Tissue factor

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Inhibition of tissue factor expression by hydroxyurea in polymorphonuclear leukocytes from patients with myeloproliferative disorders: A new effect for an old drug?'. Together they form a unique fingerprint.

Cite this