CYTOKINE-INDUCED GENERATION OF MULTINUCLEATED GIANT-CELLS INVITRO REQUIRES INTERFERON-GAMMA AND EXPRESSION OF LFA-1

Multinucleated giant cells (MGC), which are a common feature of various pathologic states, were generated in vitro by cytokine‐stimulation of human peripheral blood monocytes. As expected, conditioned medium, i.e. the supernatant of concanavalin A‐stimulated peripheral blood mononuclear cells, readily caused generation of MGC. Addition of a monoclonal antibody (mAb) against interferon‐γ (IFN‐γ) completely abrogated this effect. IFN‐γ alone, however, had a much smaller effect than the conditioned medium. All other cytokines tested [including interleukin (IL) 2, IL 4 and tumor necrosis factor‐α, which are known to activate monocytes] did not induce MGC nor did they enhance the effect of IFN‐δ. Formation of MGC could almost entirely be inhibited by mAb to the α or β chain of LFA‐1 and to a lesser extent by relatively high concentrations of a mAb against ICAM‐1, one of the ligands of LFA‐1. In contrast to the anti‐IFN‐γ mAb that had no significant effect on the formation of monocyte clusters, mAb against LFA‐1 inhibited clustering very efficiently. Antibodies directed to a number of different antigens present on the surface of monocytes (α chains of CR3 and CR4, HLA class I and II molecules, CD14 and CD16 antigens) had little or no effect on the generation of MGC. IFN‐γ, but not the concanavalin A‐induced supernatant clearly enhanced expression of LFA‐1 and ICAM‐1 on monocytes. The results indicate that cytokine‐induced generation of MGC is not possible without IFN‐γ, but most probably additional factor(s) enhance this effect. The mechanism(s) by which IFN‐γ promotes monocyte fusion apparently includes, among others, up‐regulation of LFA‐1 whose expression seems to be necessary but not sufficient for fusion. Copyright © 1990 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim