Intercellular adhesions which occur during the mononuclear phagocyte differentiation are predominantly mediated by the lymphocyte-function-associated antigen-1 (LFA-1) family and the intercellular-adhesion molecule-1 (ICAM-1) which is a ligand for LFA-1. Thus, differentiation of U-937 promonocytic cells induced by phorbol esters occurs concomitantly with intercellular LFA-l/ICAM-1 -dependent cluster formation. Since these homotypic adhesions can be inhibited by monoclonal antibodies (mAb) directed to either LFA-1 or ICAM-1, we have analyzed whether the lack of cell -cell adhesions impairs the differentiation process. Treatment of U-937 cells with the phorbol ester 12-0-tetradecanoylphorbol 13-acetate in the presence of mAb to LFA-1 or ICAM-1 antigens yielded cells free from homotypic adhesions but differentiated as evidenced by their decreased proliferation and enhanced capacity for generation of superoxide anion. In addition, expression of the C D l l c antigen was increased, whereas the transferrin receptor disappeared from the cell surface. Vimentin gene transcription was also greatly augmented as opposed to a clear diminution in the levels of c-myc and ornithine decarboxylase transcripts. These results clearly demonstrate that phorbol esters can induce differentiation of monocytic cells independently of cell -cell adhesion.Intercellular adhesions play an important role in many immunological functions. Many of the adhesion phenoma of leucocytes are mediated by the lymphocyte-function-associated antigen 1 (LFA-1) family and the intercellular-adhesion molecule 1 (ICAM-1, CD54) molecule, which is a ligand for LFA-1 [I -61. These molecules are involved in antigen presentation [2, 7, 81, T cell effector functions [9-121, cooperation between B and T lymphocytes [I31 and chemotaxis of myeloid cells [I, 14, 151. The LFA-1 family of antigens is composed of three structurally related glycoproteins, LFA-1 (CD1 la), Mol (CDllb) and p150,95 (CDllc) [16]. These three antigens are noncovalently linked a : j heterodimers which have distinct a subunits of 170, 165 and 150 kDa, respectively, and share a common j subunit of 95 kDa (CD18) [16,17].In mononuclear phagocytes, the regulation of cell -cell adhesion is an important aspect of their function and development. Thus, monocytes initiate diapedesis by adherence to the endothelium. This adhesion to endothelial cells allows the monocytes to exit from blood vessels by passing between adjacent endothelial cells. At the same time that these adhesion processes take place, monocytes maturate into tissue macrophages. Also, upon antigen challenge, there is a massive infiltration of macrophages showing homotypic (macrophage -macrophage) and heterotypic (macrophage -T-cell) interactions. These cellular associations can lead to granuloma Several markers for monocytic differentiation of myeloid cell lines have been used, such as an arrest in their proliferative capacity [23 -25, 281, variations in the levels of specific gene transcripts [26, 29 -331, changes in the expression of specific...