Lipopolysaccharide induces expression of APO2 ligand/TRAIL in human monocytes and macrophages

Monocytes express cytotoxic factors of the tumour necrosis factor (TNF) lig and superfamily, including TNF and Fas ligand, both on the cell surface and in secreted form. In this report, we show that human monocytes and monocyt e-derived macrophages stimulated with lipopolysaccharide (LPS) express APO2 ligand (APO2L, TRAIL), a recently discovered cytotoxic member of the TNF l igand superfamily. LPS increased the transcription of APO2L mRNA in monocyt es and macrophages. Flow cytometric analysis showed low surface and high in tracellular levels of APO2L, and LPS increased the expression of both. In a ddition, LPS increased the monocyte- and macrophage-mediated cytotoxicity a gainst the APO2L-sensitive Jurkat and RPMI-8226 cells. Addition of the APO2 L-binding decoy receptor 1 (DcR1)-Fc fusion protein inhibited the cytotoxic ity by 30-70%. LPS also stimulated the release of soluble APO2L from the mo nocytes and macrophages. Monocytic phagocytosis of target cells was increas ed by LPS and partially inhibited by DcR1-Fc. Taken together, these data de monstrate a novel mechanism of cytotoxicity mediated by LPS-activated human monocytes and macrophages.