title: Thrombopoietin contributes to enhanced platelet activation in cigarette smokers.
abstract: 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.
authors.affiliation: Department of Clinical Pathophysiology, University of Turin, 10126 Turin, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Lupia
authors.forename: Ornella
authors.initials: O
authors.lastname: Bosco
authors.forename: Alberto
authors.initials: A
authors.lastname: Goffi
authors.forename: Cesare
authors.initials: C
authors.lastname: Poletto
authors.forename: Stefania
authors.initials: S
authors.lastname: Locatelli
authors.forename: Tiziana
authors.initials: T
authors.lastname: Spatola
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cuccurullo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Montrucchio
mesh_terms: 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*
chemical_list: D019007:P-Selectin; D002097:C-Reactive Protein; D013926:Thrombopoietin; D003367:Cotinine