Intercellular adhesion molecule-1 in extravasation of normal mononuclear and leukaemia cells.
Interaction of intercellular adhesion molecules (ICAMs) with their receptors has a key role in normal leucocyte adhesion and migration, whereas in leukaemia this has not been well established. In this study, we have evaluated the roles of different adhesion molecules in normal and leukaemia cell extravasation in a novel organotypic model for vessel wall and measured plasma ICAM-1 and -2 levels in acute leukaemia patients at diagnosis and during chemotherapy. We found that both normal mononuclear cells and blast cells from 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 extravasation, 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 leukaemia patients and found that they correlated only weakly with the white blood cell count. No correlation was found between sICAM-1 or -2 levels and the 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 increased plasma sICAM-1 levels in leukaemia patients may not play a role in leukaemia cell infiltration. However, as we showed that ICAM-1 mediated leukaemia cell extravasation on the cell surface, it is possible that cellular ICAM-1 has an important role in disease progression.
Mustjoki
S
S
Departments of Virology, University of Helsinki, Finland. Satu.Mustjoki@helsinki.fi
Alitalo
R
R
Elonen
E
E
Carpén
O
O
Gahmberg
C G
CG
Vaheri
A
A
D015703:Antigens, CD / Q000097:blood / Q000378:metabolism; D001808:Blood Vessels; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000097:blood / Q000378:metabolism; D002465:Cell Movement; D046508:Culture Techniques; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000378:metabolism*; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood / Q000276:immunology*; D017254:Leukemic Infiltration; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D018448:Models, Immunological; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C065289:ICAM2 protein, human; D018799:Intercellular Adhesion Molecule-1