Replenishment of NO in SSRBCs reduces Epi-activated SSRBC adhesion to the endothelium and vessel occlusion in vivo. (A-K) Microscopic observations of postcapillary venules were conducted through implanted dorsal skin-fold window chambers after infusion of human SSRBCs into the tail vein of nude mice using 5× and 20× magnification. Vessels without adherent cells appear gray, due to the blurred fluorescence of rapidly moving SSRBCs. Infusion of vehicle-treated (n = 5; A-B), Epi-treated (n = 5; C-E), NO-loaded Epi-treated (n = 5; F-H), or sham-loaded Epi-treated (n = 5; I-K) human SSRBCs was performed. (A-E) Vehicle-treated human SSRBCs showed little adhesion to vessel walls (indicated by black arrows), whereas Epi-treated human SSRBCs showed marked adhesion to postcapillary venules, as indicated by black arrows, with intermittent vaso-occlusion, as indicated by white arrows. (F-K) In contrast, NO-loaded Epi-treated human SSRBCs displayed only minimal adhesion (indicated by black arrows) and no vaso-occlusion, whereas sham loading had no inhibitory effect on Epi-treated SSRBC adhesion (indicated by black arrows) and vaso-occlusion (indicated by white arrows). Scale bar, 50 μm. (L) Fluorescence intensity (pixels) represents fluorescence-labeled human SSRBC adhesion to vessel walls quantified by examining movies produced using 20× magnification. The values of segments of vessels analyzed were averaged among groups of animals to represent the mean fluorescence intensity. Error bars show SEM of 5 different experiments for each treatment. *P < .05 for either Epi-treated or sham-loaded Epi-treated vs vehicle-treated, and NO-loaded Epi-treated vs sham-loaded Epi-treated.