Human brain microvascular ECs were sham treated or treated with the NOX inhibitor apocynin (A), prior to exposure or not with sickle RBCs (SS RBCs) (n = 6). Exposure of HBMVECs to SS RBCs increased ROS generation in ECs, which is dependent on NOX. Flow cytometry analysis shows ARL13b bound to SS RBCs (n = 6) prior to (baseline) and after interaction with shear-stressed ECs pretreated with apocynin (B). *P < 0.05, and ****P < 0.0001. +a = ECs treated with apocynin. For A, 1-way ANOVA test was performed, and for B, Wilcoxon’s signed-rank test was performed.