CXCR2 blockade reduces radical formation in hyperoxia-exposed newborn rat lung.
Inflammation contributes greatly to the pathogenesis of bronchopulmonary dysplasia. In previous studies, we showed that blocking neutrophil influx by treatment with SB265610, a selective CXCR2 antagonist, could partly reduce superoxide accumulation and preserve alveolar development in 60% O(2)-exposed newborn rats. The purpose of this study was to further investigate the role of neutrophils in the formation of reactive oxygen and nitrogen species mediating hyperoxia-impaired lung development. We found that hydroxyl radical formation and lipid peroxidation in rat lungs were significantly increased during 60% O(2) exposure. These increases were attenuated by the administration of SB265610. In addition, SB265610 largely inhibited protein nitration induced by hyperoxia. SB265610 partly prevented the hyperoxia-enhanced bronchoalveolar lavage (BAL) protein content in 60% O(2)-exposed animals. Our results demonstrate that neutrophils have a pivotal role in hydroxyl radical formation, lipid peroxidation and protein nitration. Taken together with our previous studies, the present findings show that blocking neutrophil influx protects alveolar development and improves lung function in part by preventing reactive oxygen/nitrogen species accumulation.
Liao
Lingjie
L
Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Ning
Qin
Q
Li
Yuxiang
Y
Wang
Wei
W
Wang
Anru
A
Wei
Wei
W
Liu
Xin
X
Auten
Richard L
RL
Tanswell
A Keith
AK
Luo
Xiaoping
X
D000818:Animals; D000831:Animals, Newborn; D015237:Dinoprost / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D017665:Hydroxyl Radical / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D018496:Hyperoxia / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism; D010100:Oxygen / Q000633:toxicity*; D051381:Rats; D026361:Reactive Nitrogen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors* / Q000502:physiology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism
D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D023063:Receptors, Interleukin-8B; C075750:8-epi-prostaglandin F2alpha; D017665:Hydroxyl Radical; C002744:3-nitrotyrosine; D014443:Tyrosine; D015237:Dinoprost; D010100:Oxygen