Differential function of LFA-1 family molecules (CD11 and CD18) in adhesion of human monocytes to melanoma and endothelial cells

Abstract

Human peripheral blood monocytes from normal, healthy donors express the leucocyte function-associated antigen (LFA)-1, CR3 and p150,95. These heterodimeric antigens are members of a glycoprotein family sharing a common beta subunit but endowed with distinct alpha chains. They have been shown to play an important role in cell-cell interactions. In the present study we have investigated the role of these molecules in the interaction of monocytes with endothelial cells and melanoma (tumour) cells. Heterotypic cell-cell interactions were studied in single cell conjugate assays and by adhesion of monocytes to monolayers of cells. The results demonstrate that monoclonal antibodies directed against LFA-1 alpha, CR3 alpha, p150,95 alpha and the common beta chain strongly reduce the number of conjugates (71, 50, 60 and 89% inhibition, respectively), formed between monocytes and melanoma or endothelial cells in a single cell assay. In contrast, adhesion of monocytes to monolayers of the same cells seems only to depend on p150,95, since only antibodies directed to the alpha chain of this molecule and to the common beta chain inhibited adhesion. Interestingly, the number of conjugates formed with melanoma cells in single cell assays was at least twice the number of conjugates formed between monocytes and endothelial cells, whereas no differences were observed in the adhesion of monocytes to monolayers of these cells. However, the basis for this phenomenon is not yet clear. These results indicate that not only LFA-1 but also CR3 and p150,95 can mediate adhesion to target cells in suspension, but that monocyte adhesion to monolayers is caused by a different mechanism in which the p150,95 molecule seems to play a prominent role.