Verotoxin-l Promotes Leukocyte Adhesion to Cultured Endothelial Cells Under Physiologic Flow Conditions

Hemolytic uremic syndrome (HUS), which is the most common cause of acute renal failure in infants and small children, is caused by verotoxin (m)-producing Escherichia coli infection. Endothelial injury determines microvascular thrombosis and evidence is available from recent studies that suggests that leukocyte activation participates in endothelial damage. We studied here the effect of VT-1 on leukocyte adhesion to vascular endothelium under physiologic flow conditions. Human umbilical vein endothelial cells (HUVECs) were incubated for 24 hours with VT-1 (0.1, 1, and 10 pmol/ L) and then exposed t o a total leukocyte suspension in a parallel plate flow chamber under laminar flow conditions (1.5 dyneslcm’). Adherent cells were counted by digital image processing. Results showed that VT-1 dose-dependently increased the number of adhering leukocytes t o HUVECs as compared with unstimulated cells. The adhesive response elicited by VT-1 was comparable to that of interleukin-1P (IL-lp), one of the most potent inducers of endothelial cell adhesiveness. Exposure of HUVECs to VT-1 did not affect