CHARACTERIZATION OF THE ADHERENCE OF NORMAL AND LEUKEMIC CD34+ CELLS TO ENDOTHELIAL MONOLAYERS

The capacity of normal CD34+ marrow cells and CD34+ leukemic cell line s to adhere to human umbilical vein endothelial cells has been examine d. Such interactions have importance since the processes of homing and egress within the marrow microenvironment involve the traverse of sin usoidal endothelium. Umbilical vein endothelial monolayers expressed C D44 and CD54 constitutively, and expression of both E-selectin (ELAM) and vascular cell adhesion molecule-1 (VCAM-1) were inducible with int erleukin-1 (IL-1) alpha and beta and tumor necrosis factor (TNF). CD34 + marrow cells bound to unstimulated endothelial layers (33 vs. 16% to plastic), and their adhesion was significantly increased in the prese nce of IL-1 or TNF. This increased adhesion was not inhibited by funct ionally blocking antibodies to E-selectin or to CD54 but was partially inhibited by antibodies to VCAM. CD34+ KG1a cells also bound to endot helial monolayers (33 vs. 8% to plastic), and such adhesion was also u pregulated by pretreatment of the endothelial cells with IL-1 or TNF. In contrast to normal CD34+ cells, this increased adhesion was inhibit ed by antibodies to E-selectin but not to VCAM. These findings indicat e that adhesion of both normal CD34+ cells and leukemic blasts to endo thelial cells can be upregulated by inflammatory mediators such as TNF and IL-1.