Systemic inflammation may inhibit neutrophil
and promote multiple organ dysfunction syndrome. We hypothesize that severe trauma
causes dysregulation of PMN apoptosis
Neutrophils were isolated from trauma
patients (24–72 hours after injury; n = 16) and controls (healthy volunteers) and incubated for 18 hours. In separate experiments, control cells were treated ± the nuclear factor kappa beta (NFκβ) inhibitor pyrrolidinithiocarbamate then incubated with 25% patient or control plasma. Apoptosis
was quantified by enzyme-linked immunosorbent assay for histone-associated DNA and annexin V fluorescence-activated cell sorter. NFκβ activation was determined by Western blot for phosphorylated Iκβ.
was inhibited in trauma
patient PMN. Neutrophil apoptosis
correlated with multiple organ dysfunction syndrome score, Acute Physiology and Chronic Health Evaluation II, and platelet count. Patient plasma inhibited apoptosis
and induced phosphorylation of Iκβ in control cells. Inhibition of PMN apoptosis
by patient plasma was blocked by pretreatment with pyrrolidinithiocarbamate.
NFκβ-dependent inhibition of neutrophil apoptosis
occurs after trauma
. Early inhibition of PMN apoptosis
is dependent on the magnitude of injury.