MACROPHAGE-COLONY-STIMULATING FACTOR (M-CSF) STIMULATION INDUCES CELL-DEATH IN HIV-INFECTED HUMAN MONOCYTES

We show here that HIV-infected monocyte-macrophages stimulated by macrophage-colony stimulating factor (M-CSF) undergo massive syncytia formation and die. The M-CSF-stimulated HIV-infected monocyte-macrophages (M/M) destroy themselves by blebbing out particles (resembling apoptotic bodies) which may contain condensed and marginated chromatin. The death of monocyte-macrophages is also characterized by the expression of ''Tissue'' Transglutaminase (tTG) which is one of the genes specifically expressed and activated in apoptising cells. Noteworthy, when the syncytia formation and consequently death is prevented, infected monocyte-macrophages remain viable and produce large amounts of virus for an extended period. The concentrations of M-CSF (1000 U/ml) used in this work are similar to those that stimulate macrophages in vivo. This suggests that HIV killing of M/M in the presence of M-CSF could lead, in vivo, to a greater than expected loss of immune cells and may contribute to explain the complex derangement of the immune function observed in HIV-infected patients.