Thrombopoietin contributes to enhanced platelet activation in cigarette smokers.
OBJECTIVE
Thrombopoietin (TPO) is a humoral growth factor that primes platelet activation in response to several agonists. We recently showed that TPO enhances platelet activation in unstable angina and sepsis. Aim of this study was to investigate the role of TPO in platelet function abnormalities described in cigarette smokers.


METHODS
In a case-control study we enrolled 20 healthy cigarette smokers and 20 nonsmokers, and measured TPO and C-reactive protein (CRP), as well as platelet-leukocyte binding and P-selectin expression. In vitro we evaluated the priming activity of smoker or control plasma on platelet activation, and the role of TPO in this effect. We then studied the effects of acute smoking and smoking cessation on TPO levels and platelet activation indices.


RESULTS
Chronic cigarette smokers had higher circulating TPO levels than nonsmoking controls, as well as increased platelet-leukocyte binding, P-selectin expression, and CRP levels. Serum cotinine concentrations correlated with TPO concentrations, platelet-monocyte aggregates and P-selectin expression. In addition, TPO levels significantly correlated with ex vivo platelet-monocyte aggregation and P-selectin expression. In vitro, the plasma from cigarette smokers, but not from nonsmoking controls, primed platelet-monocyte binding, which was reduced when an inhibitor of TPO was used. We also found that acute smoking slightly increased TPO levels, but did not affect platelet-leukocyte binding, whereas smoking cessation induced a significant decrease in both circulating TPO and platelet-leukocyte aggregation.


CONCLUSIONS
Elevated TPO contributes to enhance platelet activation and platelet-monocyte cross-talk in cigarette smokers.
Lupia
Enrico
E
Department of Clinical Pathophysiology, University of Turin, 10126 Turin, Italy.
Bosco
Ornella
O
Goffi
Alberto
A
Poletto
Cesare
C
Locatelli
Stefania
S
Spatola
Tiziana
T
Cuccurullo
Alessandra
A
Montrucchio
Giuseppe
G
D000328:Adult; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D002449:Cell Aggregation / Q000502:physiology; D003367:Cotinine / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000502:physiology*; D012907:Smoking / Q000503:physiopathology*; D016540:Smoking Cessation; D013926:Thrombopoietin / Q000097:blood / Q000502:physiology*
D019007:P-Selectin; D002097:C-Reactive Protein; D013926:Thrombopoietin; D003367:Cotinine