Perfusion with sickle erythrocytes up-regulates ICAM-1 and VCAM-1 gene expression in cultured human endothelial cells

Sickle cell anemia is characterized by periodic vasoocclusive crises. Incre ased adhesion of sickle erythrocytes to vascular endothelium is a possible contributing factor to vasoocclusion, This study determined the effect of s ickle erythrocyte perfusion at a venous shear stress level (1 dyne/cm(2)) o n endothelial cell (EC) monolayers. Sickle erythrocytes upregulated interce llular adhesion molecule-1 (ICAM-1) gene expression in cultured human endot helial cells. This was accompanied by increased cell surface expression of ICAM-1 and also elevated release of soluble ICAM-1 molecules. Expression of vascular cell adhesion molecule-1 (VCAM-1) messenger RNA (mRNA) was also s trikingly elevated in cultured ECs after exposure to sickle cell perfusion, although increases in membrane-bound and soluble VCAM-1 levels were small, The presence of cytokine interleukin-1 beta in the perfusion system enhanc ed the production of ICAM-1 and VCAM-1 mRNA, cell surface expression, and t he concentrations of circulating forms. This is the first demonstration tha t sickle erythrocytes have direct effects on gene regulation in cultured hu man ECs under well-defined flow environments. The results suggest that perf usion with sickle erythrocytes Increases the expression of cell adhesion mo lecules on ECs and stimulates the release of soluble cell adhesion molecule s, which may serve as indicators of injury and/or activation of endothelial cells. The interactions between sickle red blood flow, inflammatory cytoki nes, and vascular adhesion events may render sickle cell disease patients v ulnerable to vasoocclusive crises. (C) 2000 by The American Society of Hema tology.