SELECTIVE ENHANCEMENT OF LEU-CAM EXPRESSION BY INTERLEUKIN-6 DURING DIFFERENTIATION OF HUMAN PROMONOCYTIC U937 CELLS

Interleukin 6 (IL-6) is a cytokine with multiple biological activities on various tissues and cells. We have investigated the effect of recombinant human IL-6 (rhIL-6) on growth and differentiation of U937. Recombinant human IL-6 induced a dose-dependent growth inhibition, apparent around day 4, of up to 50% by day 8 of culture. Concomitant with this, changes in cytochemical activities were observed, indicative of differentiation. A panel of U937 antigens was analysed after culture with rhIL-6. Expression of the majority of these membrane antigens was unaffected, with the exception of two classes. First, rhIL-6 had a profound effect on members of the leucocytic cell adhesion molecules (Leu-CAM) family. Expression of the alpha-chain of CR3 (complement receptor 3; CD11b) was enhanced in a dose-dependent fashion, with maximal expression around day 7. Parallel to this a simultaneous increase in beta-chain (CD18) expression was found. Furthermore, enhanced expression of CR3 was, accompanied by increased rosetting with sheep erythrocytes sensitized with C3bi. A much lower, but significant, enhancement was observed for the alpha-chain of the p150,95 antigen (CD11c). Expression of leucocyte function-associated antigen-1, (LFA-1), (CD11a/CD18) remained unchanged. Remarkably, however, expression of a ligand of LFA-1, intercellular adhesion molecule-1 (ICAM-1; CD54), was enhanced with similar kinetics as CR3 and p150,95. A specific anti-rhIL-6 antiserum completely inhibited the IL-6 effect. These observations provide further support for an important role of IL-6 in the regulation of myeloid cell development in man.