Figure 7.

Hydroxyurea (HU) reduces neutrophil and platelet activation via NO production. SCD mice were pretreated by intravenous injection of PTIO, a NO scavenger (1 mg/kg) 30 min prior to TNF-α challenge. Vehicle (0.01 M phosphoric acid, −) or drugs were given orally to TNF-α-challenged SCD mice as described in Figure 5. Blood and bone marrow were collected 3 h after TNF-α injection. Isolated (A, B) neutrophils and (C) platelets were treated with or without fMLP (for 10 min) or thrombin (for 5 min), respectively. Flow cytometry was performed to measure (A, B) the surface level of αMβ2 integrin and soluble fibrinogen binding in stimulated neutrophils and (C) P-selectin exposure in stimulated platelets. Data represent the mean ± SD (n = 3). *P<0.05, **P<0.01, ***P<0.001, and ****P<0.0001 versus unstimulated vehicle control (or between two groups), ANOVA and the Tukey test.