Opposing effects of 60% oxygen and neutrophil influx on alveologenesis in the neonatal rat.
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.
Yi
Man
M
Lung Biology Programme, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada.
Jankov
Robert P
RP
Belcastro
Rosetta
R
Humes
Daryl
D
Copland
Ian
I
Shek
Samuel
S
Sweezey
Neil B
NB
Post
Martin
M
Albertine
Kurt H
KH
Auten
Richard L
RL
Tanswell
A Keith
AK
D000818:Animals; D000831:Animals, Newborn; D001997:Bronchopulmonary Dysplasia; D004195:Disease Models, Animal; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000187:drug effects / Q000254:growth & development* / Q000276:immunology; D008171:Lung Diseases / Q000276:immunology / Q000503:physiopathology*; D020556:Neutrophil Infiltration / Q000276:immunology*; D010100:Oxygen / Q000276:immunology / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors* / Q000276:immunology
D017382:Reactive Oxygen Species; D023063:Receptors, Interleukin-8B; D010100:Oxygen