RBCs from patients with SCD and RBCs with altered GPA have a reduced protective effect on the endothelium. Transendothelial electrical resistance (TER) is represented at different time points over 20 hours, for human pulmonary arterial endothelial cells (HPAECs) exposed at baseline or with LPS challenge, to RBCs (1:20) from stable patients with SCD (no pain; n = 6) (A-B); from patients with SCD in pain crises (n = 8) (C-D); and from HS but treated with anti-GPA or with neuraminidase to alter GPA on the RBC surface (E-F). TER was measured with incubation of RBC samples drawn from patients either before transfusion (red triangles) or after transfusion (green Xs) (A-D), and on HS’ RBC samples treated with anti-GPA (teal triangles) or treated with neuraminidase (purple Xs) (E-F). Multiple comparisons at each time point were made between groups using one-way ANOVA with Bonferroni post hoc for statistical analysis. Significance is marked as ∗ P < .05 for comparison with HPAEC alone (blue); or as † P < .05 for comparisons with HPAEC incubated with HS’ RBCs (orange). LPS (200 ng/mL) challenge was performed at 30’ min after start of RBC incubations.