Acute myeloid leukaemia blast cells bind to human endothelium in vitro utilizing E-selectin and vascular cell adhesion molecule-1 (VCAM-1).
The adhesion of acute myeloid leukaemia (AML) blast cells to human umbilical vein endothelial cells (HUVECs) was investigated in vitro. Adhesion of blast cells from 10 cases of AML to unstimulated and interleukin-1 beta (IL-1) stimulated HUVECs was similar to or greater than that of control neutrophils. The extent to which endothelial E-selectin and vascular cell adhesion molecule-1 (VCAM-1) were involved in this adhesive process was investigated using blocking monoclonal antibodies to these proteins. In the majority of cases studied (7/8), anti-E-selectin significantly inhibited adhesion to IL-1 stimulated endothelium (26-65% inhibition) and in 5/8 cases so did anti-VCAM-1 (maximum of 31% inhibition). All cases were found to express the sialylated Lewis x antigen and very late activation antigen-4, ligands for E-selectin and VCAM-1 respectively. Our results indicate that leukaemic blast cells adhere to human endothelium and that there are E-selectin and, to a lesser extent, VCAM-1-dependent components to this process. Such adhesive interactions are likely to confer on AML blast cells the ability to migrate across the vascular wall and so to establish extravascular disease.
Cavenagh
J D
JD
Division of Haematology, St George's Hospital Medical School, London.
Gordon-Smith
E C
EC
Gibson
F M
FM
Gordon
M Y
MY
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000502:physiology*; D002478:Cells, Cultured; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology; D007951:Leukemia, Myeloid / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000502:physiology*; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007375:Interleukin-1; D009363:Neoplasm Proteins; D019010:Vascular Cell Adhesion Molecule-1