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 macr ophage-colony stimulating factor (M-CSF) undergo massive syncytia form ation and die. The M-CSF-stimulated HIV-infected monocyte-macrophages (M/M) destroy themselves by blebbing out particles (resembling apoptot ic bodies) which may contain condensed and marginated chromatin. The d eath of monocyte-macrophages is also characterized by the expression o f ''Tissue'' Transglutaminase (tTG) which is one of the genes specific ally expressed and activated in apoptising cells. Noteworthy, when the syncytia formation and consequently death is prevented, infected mono cyte-macrophages remain viable and produce large amounts of virus for an extended period. The concentrations of M-CSF (1000 U/ml) used in th is 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 contr ibute to explain the complex derangement of the immune function observ ed in HIV-infected patients.