The persistence of a neutrophil-mediated inflammatory response is due in part to a delay in their spontaneous rates of apoptosis or cell death. Regulating apoptosis has important implications for the resolution of inflammatory disorders, such as the systemic inflammatory response syndrome or acute respiratory distress syndrome. Neutrophils through their primary function of killing bacteria generate large concentrations of reactive oxygen intermediates and have alterations in the levels of antioxidants. Reactive oxygen intermediates and antioxidants are important regulators of the apoptotic caspases, but the mechanisms involved are still under debate and investigation. This review addresses the role of the cellular redox status of neutrophils on the apoptotic cascade leading to cell death.
Labor is a mild proinflammatory state that is associated with fetal leukocytosis. Elective cesarean section has been linked with increased neonatal morbidity, which may be partially immune mediated. We hypothesized that labor may alter neutrophil phenotype and thereby decrease neonatal complications. We characterized neutrophil function and survival in normal neonates after either uncomplicated vaginal delivery (VD) or elective cesarean section (CS) without labor. Spontaneous neutrophil apoptosis is delayed in cord blood neutrophils of neonates after normal labor (VD) compared with CS, as assessed by propidium iodide DNA incorporation using flow cytometry. This demonstrates their ability to maintain an inflammatory response. CD11b expression on neonatal neutrophils after CS is decreased, providing further evidence of altered activation or priming. Lipopolysaccharide responsiveness, characterized by CD11b and apoptosis, is similar in VD and adults, but CS-derived neutrophils are unresponsive. Baseline TLR-4 levels are elevated in CS in contrast to the other groups, although expression is not up-regulated by lipopolysaccharide co-incubation. Neonatal neutrophil survival and function are altered by labor and may increase antibacterial function and neutrophilia. This suggests that labor of any duration may be immunologically beneficial to the normal term neonate.
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