Abstract
Neutrophil apoptosis is impaired in neonates, and this contributes to prolonged inflammation and tissue injury in infants after infection or trauma. In the present studies, we investigated whether labor generates mediators that further suppress apoptosis. We found that neutrophil apoptosis was reduced in neonates exposed to labor, when compared with infants delivered by cesarean section before labor. This was not due to alterations in caspase-3 or inhibitor of apoptosis protein-2 (IAP-2). In contrast, labor primed neutrophils to express tumor necrosis factor α (TNF-α), suggesting that proinflammatory mediators contribute to reduced apoptosis after labor. Eicosanoids generated via cyclooxygenase-2 (Cox-2) and lipoxygenase (Lox) also regulate neutrophil apoptosis. 15-Lox, which generates proapoptotic lipoxins, but not Cox-2, was greater in neutrophils before labor, relative to cells exposed to labor. Anti-inflammatory eicosanoids exert their effects in part via peroxisome proliferator–activated receptor γ (PPAR-γ). Expression of gelatinase-associated lipocalin and catalase, two markers of PPAR-γ activity, were increased in neonatal neutrophils before labor, relative to cells exposed to labor. These findings suggest that the anti-inflammatory environment is maintained before labor, in part, by eicosanoids. Although increased neutrophil longevity after labor is important for host defense in the immediate newborn period, it may contribute to inflammatory or oxidative injury in susceptible infants.
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Abbreviations
- Cox-2:
-
cyclooxygenase-2
- DCF-DA:
-
5- (and -6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate acetyl ester
- IAP-2:
-
inhibitor of apoptosis protein-2
- Lox:
-
lipoxygenase
- N-Gal:
-
neutrophil gelatinase-associated lipocalin
- PMA:
-
phorbol 12-myristate 13-acetate
- PPAR-γ:
-
peroxisome proliferator–activated receptor γ
- ROIs:
-
reactive oxygen intermediates
- SOD:
-
superoxide dismutase
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Supported by National Institutes of Health grants HD042036, ES005022, GM034310, ES004738, HL067708, and CA100994.
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Weinberger, B., Vetrano, A., Syed, K. et al. Influence of Labor on Neonatal Neutrophil Apoptosis, and Inflammatory Activity. Pediatr Res 61, 572–577 (2007). https://doi.org/10.1203/pdr.0b013e318045be38
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DOI: https://doi.org/10.1203/pdr.0b013e318045be38
