Effects of Ibuprofen and Hypoxia on Neutrophil Apoptosis in Neonates
Effects of Ibuprofen and Hypoxia on Neutrophil Apoptosis in Neonates
复制标题
布洛芬和缺氧对新生儿中性粒细胞凋亡的影响
作者：
N. Hanna;S. Graboski;D. Laskin;B. Weinberger
背景：伊曲康是一种环氧合酶抑制剂，对治疗早产儿动脉导管未闭有效。然而，最近的试验表明，它可能会增加患坏死性小肠结肠炎和慢性肺病的风险。新生儿中性粒细胞凋亡受损，导致活化细胞清除率降低，并可能导致婴儿对这些炎性疾病的易感性。目的：在目前的研究中，我们调查的假设，布洛芬减少缺氧或脂多糖（LPS）的设置新生儿中性粒细胞凋亡。研究方法：从成人和脐带血中分离中性粒细胞和外周血单核细胞，并在存在或不存在布洛芬（1.5mM）、缺氧（<5%O2）和细菌LPS（100 ng/ml）的情况下培养。通过使用流式细胞术测量FITC-膜联蛋白V的结合来定量细胞凋亡。通过ELISA测量细胞上清液中的细胞因子浓度。结果：24 h后，20%的成人和14%的新生儿中性粒细胞发生凋亡。在成人和新生儿细胞的细胞凋亡减少缺氧。Iceland进一步减少中性粒细胞凋亡，但仅当细胞在混合白细胞存在下培养时。这表明布洛芬对细胞凋亡的影响依赖于外周血单个核细胞分泌的可溶性产物。我们发现，布洛芬可显著增加新生儿白细胞产生肿瘤坏死因子（TNF）-α，并且在LPS和缺氧存在下暴露于布洛芬后进一步增加。相反，巨噬细胞炎性蛋白（MIP）-1α的产生不受布洛芬治疗的影响，布洛芬阻断了LPS对这种趋化因子的诱导。结论：布洛芬对中性粒细胞的净效应是抗凋亡，尤其是在缺氧或LPS存在下。这种效应可能部分通过外周血单核细胞产生的TNF-α增加来介导。这些数据表明，在存在感染和/或组织灌注不足/缺氧的情况下，用布洛芬治疗婴儿可能有助于炎症性疾病的发展。
Background: Ibuprofen is a cyclooxygenase inhibitor that is effective in treating patent ductus arteriosus in preterm infants. However, recent trials have suggested that it may increase the risk of developing necrotizing enterocolitis and chronic lung disease. Apoptosis of neutrophils is impaired in newborns, leading to reduced clearance of activated cells and possibly contributing to the susceptibility of infants to these inflammatory diseases. Objectives: In the present studies, we investigated the hypothesis that ibuprofen reduces neonatal neutrophil apoptosis in the setting of hypoxia or lipopolysaccharide (LPS). Methods: Neutrophils and peripheral blood mononuclear cells were isolated from adult and cord blood and cultured in the presence or absence of ibuprofen (1.5 mM), hypoxia (<5% O2), and bacterial LPS (100 ng/ml). Apoptosis was quantified by measuring binding of FITC-Annexin V using flow cytometry. Cytokine concentrations in cell supernatants were measured by ELISA. Results: After 24 h, 20% of adult and 14% of neonatal neutrophils were apoptotic. Apoptosis was reduced by hypoxia in both adult and neonatal cells. Ibuprofen further reduced neutrophil apoptosis, but only when the cells were cultured in the presence of mixed leukocytes. This suggests that the effects of ibuprofen on apoptosis are dependent on soluble products secreted by peripheral blood mononuclear cells. We found that production of tumor necrosis factor (TNF)-α by neonatal leukocytes was significantly increased by ibuprofen, and was further increased following exposure to ibuprofen in the presence of LPS and hypoxia. In contrast, production of macrophage inflammatory protein (MIP)-1α was not affected by treatment with ibuprofen, and ibuprofen blocked induction of this chemokine by LPS. Conclusion: We conclude that the net effect of ibuprofen on neutrophils is antiapoptotic, especially in the presence of hypoxia or LPS. This effect may be mediated, in part, by increased production of TNF-α by peripheral blood mononuclear cells. These data suggest that treatment of infants with ibuprofen, in the presence of infection and/or tissue hypoperfusion/hypoxia, may contribute to the development of inflammatory diseases.
急性脓毒症期间的组胺受体拮抗剂、环氧合酶阻断剂和肿瘤坏死因子。
DOI：
10.1097/00024382-199802000-00003
发表时间：
1998
期刊：
Shock (Augusta, Ga.)
影响因子：
--
作者：
Leeper-Woodford,SK;Carey,D;Byrne,K;Walsh,C;Fisher,B;Sugerman,HJ;Fowler,AA
通讯作者：
Fowler,AA
DOI：
10.1016/s0360-3016(02)02889-4
发表时间：
2002-08
期刊：
International journal of radiation oncology, biology, physics
影响因子：
--
作者：
T. Shah;S. Ryu;Ho Jun Lee;Stephen Brown;J. H. Kim
通讯作者：
T. Shah;S. Ryu;Ho Jun Lee;Stephen Brown;J. H. Kim
影响因子：
3.8
作者：
Leuenroth, SJ;Grutkoski, PS;Simms, HH
通讯作者：
Simms, HH