Inhibition of tissue factor expression by hydroxyurea in polymorphonuclear leukocytes from patients with myeloproliferative disorders: a new effect for an old drug?
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.
Maugeri
N
N
Laboratory of Cell Biology and Pharmacology of Thrombosis, Research Laboratories, Catholic University, Campobasso, Italy. normamaugeri2003@yahoo.it
Giordano
G
G
Petrilli
M P
MP
Fraticelli
V
V
de Gaetano
G
G
Cerletti
C
C
Storti
S
S
Donati
M B
MB
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*
D005343:Fibrinolytic Agents; D019007:P-Selectin; D013925:Thromboplastin; D006918:Hydroxyurea