Opposing effects of 60% oxygen and neutrophil influx on alveologenesis in the neonatal rat.
Opposing effects of 60% oxygen and neutrophil influx on alveologenesis in the neonatal rat.
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DOI：
10.1164/rccm.200402-215oc
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发表时间：
2004-12
影响因子：
24.7
通讯作者：
M. Yi;R. Jankov;R. Belcastro;Daryl Humes;I. Copland;Samuel Shek;N. Sweezey;M. Post;K. Albertine;R. Auten;A. Tanswell
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文献类型：
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作者：
M. Yi;R. Jankov;R. Belcastro;Daryl Humes;I. Copland;Samuel Shek;N. Sweezey;M. Post;K. Albertine;R. Auten;A. Tanswell
暴露在60%氧气中14天的新生大鼠的肺发生了与人类支气管肺发育不良(BPD)相似的形态上的损伤。中性粒细胞进入肺作为炎症反应的一部分，可能在BPD的发生发展中起关键作用。一种中性粒细胞趋化因子，细胞因子诱导的中性粒细胞趋化因子-1，通过中性粒细胞CXC趋化因子受体-2发出信号，在暴露于60%氧气的新生大鼠的肺组织中增加。本研究旨在通过选择性CXC趋化因子受体-2拮抗剂SB265610抑制中性粒细胞内流，探讨中性粒细胞在BPD大鼠模型中的作用。SB265610可完全抑制新生大鼠中性粒细胞内流。它还可减轻暴露于60%氧气4天后新生大鼠肺组织中活性氧的产生。肺形态计量学分析显示，与暴露在空气中的新生大鼠相比，60%氧气持续14天，并辅以SB265610防止中性粒细胞聚集的治疗，可增加肺泡的形成。这些数据表明，如果出生后肺部炎症被抑制，新生儿肺暴露在中度高氧下可能会促进出生后肺的生长。
The lungs of newborn rats exposed to 60% oxygen for 14 days develop an injury that shares morphologic similarities to human bronchopulmonary dysplasia (BPD). Neutrophil influx into the lung, as part of an inflammatory response, may play a pivotal role in the development of BPD. A neutrophil chemokine, cytokine-induced neutrophil chemoattractant-1, which signals through the neutrophil CXC chemokine receptor-2, is increased in the lung tissue of newborn rats exposed to 60% oxygen. The purpose of this study was to explore the role of neutrophils in the rat model of BPD by inhibiting neutrophil influx using SB265610, a selective CXC chemokine receptor-2 antagonist. SB265610, administered to 60% oxygen-exposed newborn rats from birth to 14 days, completely inhibited neutrophil influx. It also attenuated increased production of reactive oxygen species in newborn rat lung tissue after exposure to 60% oxygen for 4 days. Lung morphometric analysis revealed that 60% oxygen for 14 days, when accompanied by treatment with SB265610 to prevent neutrophil accumulation, increased alveolar formation over that seen in newborn rats exposed to air. These data suggest that exposure of the neonatal lung to moderate hyperoxia may enhance postnatal lung growth, provided postnatal pulmonary inflammation is suppressed.