Hematopoietic Cell-Type-Dependent Regulation of Leukocyte Integrin Functional Activity: CD11b and CD11c Expression Inhibits LFA-1-Dependent Aggregation of Differentiated U937 Cells

To study the influence of the cellular environment on the functional activity of leukocyte integrins and to analyze their involvement in hematopoietic cell differentiation, we have developed stable transfectants of LFA-1, Mac-1, and p150,95 (CD11a-c/CD18) leukocyte integrins in cultured cell lines whose differentiation can be induced in vitro. As on circulating leukocytes, the integrins expressed on U937 or K562 cells were expressed in a constitutively inactive state, as demonstrated by the lack of adhesion to their cellular counterreceptors or soluble ligands, the absence of CD18-dependent intercellular aggregation, and their inability to mediate adhesion to protein-coated plates. However, while leukocyte integrin adhesive functions in U937 cells were induced upon treatment with cellular agonists (e.g., PMA), their function in K562 cells could be up-regulated only with activating monoclonal antibodies, demonstrating the cell-type-specific regulation of the adhesive capabilities of the three leukocyte integrins in hematopoietic cellular environment. On the other hand, the expression of either CD11/CD18 or CD11c/CD18 in U937 myeloid cells before induction of differentiation greatly affected the adhesive phenotype of differentiating cells by abrogating the CD11a/CD18-CD54-dependent homotypic aggregation. Unlike that of mock-transfected U937 cells, differentiation of CD11b/CD18- or CD11c/CD18-transfected U937 cells led to cell adhesion and spreading on the tissue culture plates, with an almost total absence of homotypic aggregates. These results confirm the role of CD11b/CD18 and CD11c/CD18 in myeloid cell adhesion and spreading and suggest that the CD11b/- and CD11c/CD18-mediated recognition of substrate-bound ligands competes or interferes with LFA-1-dependent intercellular