HYPOXIA PROLONGS NEUTROPHIL SURVIVAL IN-VITRO

Neutrophil apoptosis represents a major mechanism involved in the reso lution of inflammation. Since hypoxia induces apoptosis in several cel l lines and is of particular relevance in many disease states, we stud ied the effect of oxygen concentration on neutrophil survival in vitro . Hypoxia caused a dramatic decrease in neutrophil apoptosis (% apopto sis 20 h: 78.7 +/- 2.2% in 21% O-2, 61.4 +/- 6.5% in 2.5% O-2, 23.1 +/ - 3.2% in 0% O-2, n = 5). This was additive to the effect of GM-CSF (5 0 U/ml), not associated with induction of bcl-2 expression, and was no t mimicked by methionine (5 mM), superoxide dismutase (200 mu g/ml) or Trolox (10 mM) but was mimicked by catalase (250 mu g/ml). Hence, hyp oxia has a bcl-2-independent effect on neutrophil apoptosis that may a dversely affect the clearance of these cells from an inflammatory focu s.