A. Molloy et al., APOPTOSIS, BUT NOT NECROSIS, OF INFECTED MONOCYTES IS COUPLED WITH KILLING OF INTRACELLULAR BACILLUS-CALMETTE-GUERIN, The Journal of experimental medicine, 180(4), 1994, pp. 1499-1509
We have examined the effect of killing of host monocytes infected with
bacillus Calmette-Guerin (BCG) on the viability of the intracellular
mycobacteria. Peripheral blood monocytes were infected in vitro with a
single bacillus per cell and maintained in culture for 6-8 d to allow
the bacilli to replicate. Replicating viable BCG were found singly in
perinuclear vacuoles bounded by tightly apposed lipid bilayers. Monoc
ytes were then exposed to toxic mediators that induced killing of cell
s as evaluated by Cr-51 release into the culture medium. Both hydrogen
peroxide (H2O2) (an inducer of cell necrosis) and adenosine triphosph
ate (ATP(4-)) (an inducer of cell apoptosis) treatment killed infected
monocytes. H2O2-induced killing had no effect on BCG viability. ATP-i
nduced cell death was accompanied by DNA fragmentation and nuclear con
densation. Apoptosis was associated with a swelling of the phagocytic
vacuoles which became multibacillary and with a reduction of BCG viabi
lity as enumerated by colony-forming units.