Hypoxia prolongs neutrophil survival in vitro

AbstractNeutrophil apoptosis represents a major mechanism involved in the resolution of inflammation. Since hypoxia induces apoptosis in several cell lines and is of particular relevance in many disease states, we studied the effect of oxygen concentration on neutrophil survival in vitro. Hypoxia caused a dramatic decrease in neutrophil apoptosis (% apoptosis 20 h: 78.7 ± 2.2% in 21% O2, 61.4 ± 6.5% in 2.5% O2, 23.1 ± 3.2% in 0% O2, n = 5). This was additive to the effect of GM-CSF (50 U/ml), not associated with induction of bcl-2 expression, and was not mimicked by methionine (5 mM), superoxide dismutase (200 μg/ml) or Trolox (10 mM) but was mimicked by catalase (250 μg/ml). Hence, hypoxia has a bcl-2-independent effect on neutrophil appoptosis that may adversely affect the clearance of these cells from an inflammatory focus