RED-BLOOD-CELLS FROM PATIENTS WITH SICKLE-CELL DISEASE EXHIBIT AN INCREASED ADHERENCE TO CULTURED ENDOTHELIUM PRETREATED WITH TUMOR-NECROSIS-FACTOR (TNF)

Red blood cells (RBCs) from 24 patients with sickle cell disease were more adherent to cultured endothelium pretreated with the inflammatory cytokine, tumour necrosis factor (TNF) than RBCs from 22 healthy subjects. The enhanced sticking was apparent in RBC preparations from patients who were in crisis (mean 190% increase from controls) and out of crisis (mean 220% increase) and was not related to the number of circulating RBCs, reticulocytes, platelets, leucocytes or haemoglobin levels. When irreversibly sickled RBCs, enriched by centrifugation on density gradients, were added to TNF-treated endothelium they were found to be significantly more adherent (mean 411% increase; P<0.001) than the unfractionated RBCs from the same patients. There was no difference between the adherent properties of sickle RBCs and normal RBCs for untreated endothelium. Contributing factors to the enhanced adhesion to TNF-treated endothelium may be the low surface change of sickle RBCs, and increased levels of fibrinogen and von Willebrand's factor (vWF) in the patients' plasma. By acting on vascular endothelium to increase its adhesiveness for sickled RBCs, it is concluded that inflammatory cytokines such as TNF may have a prominent role in mediating the events that lead to microvascular occlusions in sickle cell disease.