UPMODULATION OF MULTINUCLEATED CELL-FORMATION IN LONG-TERM HUMAN BONE-MARROW CULTURES BY LEUKEMIA INHIBITORY FACTOR (LIF)

Inflammatory processes are mediated by many cellular events involving different cell types (leukocytes, monocytes, stromal cells, etc.), Num erous soluble mediators regulate these reactions, including leukaemia inhibitory factor (LIF), a cytokine which may play an important role i n inducing acute-phase protein synthesis by hepatocytes during inflamm ation. This study was designed to determine the effects of LIF on the human monocyte/macrophage lineage and provide a better definition of i ts behaviour during systemic inflammation, In-vitro exposure of human long-term bone marrow cultures to recombinant human LIF significantly increased (about two-fold) the number of multinucleated cells (MNC) fo rmed after three weeks of culture, These LIF-induced MNC expressed tar trate-resistant acid phosphatase, and LIF increased this intracellular activity by about 50%, MNC displayed phagocytotic activity but were u nable to degrade sperm whale dentin or respond to human calcitonin, Th ey did not possess the main characteristics of osteoclasts and were in fact macrophage polykaryons. Our results demonstrate for the first ti me that LIF can induce macrophage polykaryon formation from human bone marrow culture, suggesting that this factor not only produces leukocy tes but also has a direct influence on the monocyte/macrophage lineage . (C) 1997 Academic Press Limited.