Intercellular adhesion molecule-1 in extravasation of normal mononuclear and leukaemia cells

Interaction of intercellular adhesion molecules (ICAMs) with their receptor s has a key role in normal leucocyte adhesion and migration, whereas in leu kaemia this has not been well established. In this study, we have evaluated the roles of different adhesion molecules in normal and leukaemia cell ext ravasation in a novel organotypic model for vessel wall and measured plasma ICAM-1 and -2 levels in acute leukaemia patients at diagnosis and during c hemotherapy. We found that both normal mononuclear cells and blast cells fr om acute leukaemia patients, as well as retinoic acid-treated promyelocytic leukaemia cells, rapidly extravasated through endothelial cell layers into the underlying collagen matrix. ICAM-1 antibody prevented the extravasatio n, while antibodies to other adhesion molecules showed little (CD18, ICAM-2 ) or no inhibition (CD11a and ICAM-3). Soluble ICAM-1 (sICAM-1) protein had no effect. We also observed increased plasma sICAM-1 and -2 levels in leuk aemia patients and found that they correlated only weakly with the white bl ood cell count. No correlation was found between sICAM-1 or -2 levels and t he response to therapy. Although elevated sICAM-2 levels decreased rapidly during chemotherapy, sICAM-1 levels did not. Because sICAM-1 protein had no effect on leukaemia cell extravasation in vitro, it is probable that the i ncreased plasma sICAM-1 levels in leukaemia patients may not play a role in leukaemia cell infiltration. However, as we showed that ICAM-1 mediated le ukaemia cell extravasation on the cell surface, it is possible that cellula r ICAM-1 has an important role in disease progression.