The central paradigm says that during
inflammation, after completing their function, granulocytes die apoptotically in periphery to avoid destruction of self-tissues. Here we aimed to investigate the kinetic aspect of inflammatory leukocyte apoptosis and verify whether apart from neutrophils also other inflammatory leukocytes numerously undergo apoptosis. We observed that in physiological conditions, less than 7% of either resident peritoneal macrophages or lymphocytes die apoptotically. The studies on a model of acute
zymosan-induced peritoneal
inflammation revealed that there are two waves of inflammatory leukocyte apoptosis. The first wave corresponds to the time of maximal neutrophil accumulation in peritoneum (6h) and the apoptotic death indeed concerns mostly neutrophils (over 30% of those cells), but also more macrophages die at this time (>10%). The second wave (at 3 days) concerns mostly macrophages (20% versus 3-6% for other populations) and coincides with the resolution of
inflammation and the dominant presence of macrophages. In contrast, numbers of apoptotic T (1-3%) and B (approximately 5%) cells do not significantly change during the whole
peritonitis. The two waves of apoptosis concur with an increase of
caspase-8, -9 and -3 at the transcript and activity levels. The apoptosis inducer
TNF-alpha is produced only during first hours while
nitric oxide throughout all
inflammation. Moreover, during the whole course of
peritonitis the expression of pro-apoptotic Bax dominates over anti-apoptotic Bcl-2. In conclusion, we characterized kinetics of apoptotic death of inflammatory leukocytes during acute peritoneal
inflammation and revealed that both phagocyte populations (neutrophils and macrophages) die numerously in peritoneum.