Erythrocyte-endothelial cell adherence in sickle cell disorders

Area of Science:

• Hematology
• Vascular Biology
• Cellular Adhesion

Background:

• Sickle cell disease is characterized by abnormal hemoglobin S, leading to erythrocyte rigidity and vaso-occlusion.
• Erythrocyte-endothelial cell interactions are crucial in understanding the pathophysiology of sickle cell disease.

Purpose of the Study:

• To quantify the adherence of sickle erythrocytes to endothelial cells under physiologically relevant shear forces.
• To investigate the role of non-irreversibly sickled cells (non-ISC) in endothelial cell adhesion.

Main Methods:

• Utilized a fluid-shearing technique to detach sickle erythrocytes from cultured endothelial cell monolayers.
• Measured erythrocyte attachment at shear forces mimicking in vivo circulation.

Main Results:

• Non-irreversibly sickled cells demonstrated significantly higher adherence to endothelial cells compared to control cells at normal oxygen tensions.
• A notable percentage of non-ISC remained attached at shear forces exceeding physiological levels, with immediate reattachment observed.
• Plasma from sickle crisis patients further enhanced erythrocyte-endothelial cell attachment.

Conclusions:

• Sickle erythrocytes exhibit increased adhesion to endothelial cells, especially in low shear stress environments.
• This enhanced adhesion and subsequent reattachment of sickle erythrocytes contribute to vascular occlusion in sickle cell disease.
• Sickle erythrocyte-endothelial cell interactions are a significant factor in the initiation of vaso-occlusive events.