PHORBOL-MYRISTATE ACETATE-DIFFERENTIATED THP-1 CELLS DISPLAY INCREASED LEVELS OF MHC CLASS-I AND CLASS-II MESSENGER-RNA AND INTERFERON-GAMMA-INDUCIBLE TUMORICIDAL ACTIVITY

The protein kinase C activators phorbol 12-myristate 13-acetate (PMA) and mezerein induce differentiation of human monocytic leukemia (THP-1 ) cells along the monocyte/macrophage pathway of development. The diff erentiated cells express many important macrophage functions including phagocytosis and the secretion of immunomodulatory cytokines. Mezerei n-differentiated THP-1 cells secrete interleukin-1beta as well as a tu mor cell growth inhibitory factor whose basal level is increased in re sponse to interferon-gamma. However, tumoricidal, as opposed to tumori static, activity of differentiated THP-1 has not been documented. We r eport herein that PMA-differentiated THP-1 cells (PD/THP-1) contain el evated levels of MHC class I and class II mRNAs even in the absence of activating factors, and kill HT-29 human colon carcinoma cells when s timulated with recombinant human interferon-gamma. These two character istics are important components of the macrophage phenotype. The resul ts presented in this study extend previous observations on THP-1 cells by demonstrating that PD/THP-1 cells display a critical, immunologica lly relevant macrophage function, and therefore, enhance the utility o f THP-1 as a model for the in vitro study of immunomodulatory drugs an d macrophage-mediated cytocidal processes.