Sickle cell disease serum induces NADPH enzyme subunit expression and oxidant production in leukocytes

Oxidative stress plays a significant role in sickle cell disease (SCD), contributing to haemolysis, vaso-occlusive processes and endothelial dysfunction. To study the effects that the serum of SCD individuals has on the oxidative state of blood cells, sera were pooled from control individuals, steady-state SCD patients and SCD patients on hydroxyurea therapy (SCDHU), and their effects on markers of oxidative stress and damage in neutrophils isolated from healthy individuals observed. Incubation of control neutrophils, but not platelets nor red blood cells, with SCD serum (10% v/v; 2 hours) significantly augmented their production of reactive oxygen species (ROS). Increased ROS production in SCD serum-incubated neutrophils was associated with increased superoxide anion generation, apoptosis and increased nicotinamide adenine dinucleotide phosphate oxidase subunit expression. Although serum from SCDHU individuals also induced ROS generation in neutrophils, its oxidative capacity appeared to be lower. Results suggest that factors in the serum of SCD individuals contribute to ROS generation and oxidative damage in leukocytes.