Add like
Add dislike
Add to saved papers

Red Blood Cell Adhesion to Heme-Activated Endothelial Cells Reflects Clinical Phenotype in Sickle Cell Disease.

In sickle cell disease (SCD), 'disease severity' associates with increased RBC adhesion to quiescent endothelium, but the impact on activated endothelium is not known. Increased concentrations of free heme result from intravascular hemolysis in SCD. Heme is essential for aerobic metabolism, and plays an important role in numerous biological processes. Excess free heme induces reactive oxygen species generation and endothelial activation, which are associated with cardiovascular disorders including atherosclerosis, hypertension, and thrombosis. Here, we utilized an endothelialized microfluidic platform (Endothelium-on-a-chip) to assess adhesion of sickle hemoglobin-containing red blood cells (HbS RBCs), from adults with homozygous SCD, to heme-activated human endothelial cells (EC) in vitro. Confluent EC monolayers in microchannels were treated with pathophysiologically relevant levels of heme in order to simulate the highly hemolytic intravascular milieu seen in SCD. RBC adhesion to heme-activated ECs varied from subject to subject, and was associated with plasma markers of hemolysis (LDH) and reticulocytosis, thereby linking those RBCs that are most likely to adhere with those that are most likely to hemolyze. These results re-emphasize the critical contribution made by heterogeneous adhesive HbS RBCs to the pathophysiology of SCD. We found that adhesion of HbS RBCs to heme-activated ECs varied amongst individuals in the study population, and associated with biomarkers of hemolysis and inflammation, age, and a recent history of transfusion. Importantly, the microfluidic approach described herein holds promise as a clinically feasible Endothelium-on-a-chip platform with which to study complex heterocellular adhesive interactions in SCD. This article is protected by copyright. All rights reserved.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app