title: Inhibition of tissue factor expression by hydroxyurea in polymorphonuclear leukocytes from patients with myeloproliferative disorders: a new effect for an old drug?
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 microm). 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.
authors.affiliation: Laboratory of Cell Biology and Pharmacology of Thrombosis, Research Laboratories, Catholic University, Campobasso, Italy. normamaugeri2003@yahoo.it
authors.forename: N
authors.initials: N
authors.lastname: Maugeri
authors.forename: G
authors.initials: G
authors.lastname: Giordano
authors.forename: M P
authors.initials: MP
authors.lastname: Petrilli
authors.forename: V
authors.initials: V
authors.lastname: Fraticelli
authors.forename: G
authors.initials: G
authors.lastname: de Gaetano
authors.forename: C
authors.initials: C
authors.lastname: Cerletti
authors.forename: S
authors.initials: S
authors.lastname: Storti
authors.forename: M B
authors.initials: MB
authors.lastname: Donati
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002449:Cell Aggregation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology* / Q000627:therapeutic use; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000188:drug therapy* / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D010973:Platelet Adhesiveness / Q000187:drug effects; D012016:Reference Values; D013925:Thromboplastin / Q000378:metabolism*
chemical_list: D005343:Fibrinolytic Agents; D019007:P-Selectin; D013925:Thromboplastin; D006918:Hydroxyurea