Characterization of the adherence of normal and leukemic CD34+ cells to endothelial monolayers.

The capacity of normal CD34+ marrow cells and CD34+ leukemic cell lines to adhere to human umbilical vein endothelial cells has been examined. Such interactions have importance since the processes of homing and egress within the marrow microenvironment involve the traverse of sinusoidal endothelium. Umbilical vein endothelial monolayers expressed CD44 and CD54 constitutively, and expression of both E-selectin (ELAM) and vascular cell adhesion molecule-1 (VCAM-1) were inducible with interleukin-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 presence of IL-1 or TNF. This increased adhesion was not inhibited by functionally blocking antibodies to E-selectin or to CD54 but was partially inhibited by antibodies to VCAM. CD34+ KG1a cells also bound to endothelial monolayers (33 vs. 8% to plastic), and such adhesion was also upregulated by pretreatment of the endothelial cells with IL-1 or TNF. In contrast to normal CD34+ cells, this increased adhesion was inhibited by antibodies to E-selectin but not to VCAM. These findings indicate that adhesion of both normal CD34+ cells and leukemic blasts to endothelial cells can be upregulated by inflammatory mediators such as TNF and IL-1.