Published ahead of print on September 3, 2004, doi:10.1164/rccm.200402-215OC
Am. J. Respir. Crit. Care Med., Volume 170, Number 11, December 2004, 1188-1196
A more recent version of this article appeared on December 1, 2004
Submitted on March 2, 2004
Accepted on August 29, 2004
Opposing Effects of 60% Oxygen and Neutrophil Influx on Alveologenesis in the Neonatal Rat
Man Yi1, Robert P Jankov1, Rosetta Belcastro1, Daryl Humes1, Ian Copland1, Samuel Shek1, Neil B Sweezey1, Martin Post1, Kurt H Albertine2, Richard L Auten3, and A. Keith Tanswell1*
1 Lung Biology Programme, Departments of Pediatrics and Physiology, Hospital for Sick Children Research Institute and Canadian Institutes of Health Research, Toronto, ON, Canada,
2 Departments of Pediatrics, Medicine, Neurobiology and Anatomy, University of Utah, Salt Lake City, UT, USA,
3 Division of Neonatal Medicine, Department of Pediatrics, Duke University Medical Center, Neonatal Perinatal Research Institute, Durham, NC, USA
* To whom correspondence should be addressed. E-mail: keith.tanswell{at}sickkids.ca.
The lungs of newborn rats exposed to 60% oxygen for 14 days develop an injury which shares morphologic similarities to human bronchopulmonary dysplasia. Neutrophil influx into the lung, as part of an inflammatory response, may play a pivotal role in the development of bronchopulmonary dysplasia. 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 bronchopulmonary dysplasia 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.
Key words: lung injury, inflammatory response, bronchopulmonary dysplasia, CXC chemokine receptor-2, myeloperoxidase
This article has been cited by other articles:
|
|
|
|
 
A. Masood, M. Yi, M. Lau, R. Belcastro, S. Shek, J. Pan, C. Kantores, P. J. McNamara, B. P. Kavanagh, J. Belik, et al.
Therapeutic effects of hypercapnia on chronic lung injury and vascular remodeling in neonatal rats
Am J Physiol Lung Cell Mol Physiol,
November 1, 2009;
297(5):
L920 - L930.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. G. Kallapur, T. J. M. Moss, R. L. Auten Jr., I. Nitsos, J. J. Pillow, B. W. Kramer, D. Y. Maeda, J. P. Newnham, M. Ikegami, and A. H. Jobe
IL-8 signaling does not mediate intra-amniotic LPS-induced inflammation and maturation in preterm fetal lamb lung
Am J Physiol Lung Cell Mol Physiol,
September 1, 2009;
297(3):
L512 - L519.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. L. Auten, S. N. Mason, K. M. Auten, and M. Brahmajothi
Hyperoxia impairs postnatal alveolar epithelial development via NADPH oxidase in newborn mice
Am J Physiol Lung Cell Mol Physiol,
July 1, 2009;
297(1):
L134 - L142.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Boucherat, M.-L. Franco-Montoya, C. Thibault, R. Incitti, B. Chailley-Heu, C. Delacourt, and J. R. Bourbon
Gene expression profiling in lung fibroblasts reveals new players in alveolarization
Physiol Genomics,
December 19, 2007;
32(1):
128 - 141.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Irwin, K. Helm, N. Campbell, M. Imamura, K. Fagan, J. Harral, M. Carr, K. A. Young, D. Klemm, S. Gebb, et al.
Neonatal lung side population cells demonstrate endothelial potential and are altered in response to hyperoxia-induced lung simplification
Am J Physiol Lung Cell Mol Physiol,
October 1, 2007;
293(4):
L941 - L951.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. L. Auten, S. N. Mason, M. H. Whorton, W. R. Lampe, W. M. Foster, R. N. Goldberg, B. Li, J. S. Stamler, and K. M. Auten
Inhaled Ethyl Nitrite Prevents Hyperoxia-impaired Postnatal Alveolar Development in Newborn Rats
Am. J. Respir. Crit. Care Med.,
August 1, 2007;
176(3):
291 - 299.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Bry, J. A. Whitsett, and U. Lappalainen
IL-1beta Disrupts Postnatal Lung Morphogenesis in the Mouse
Am. J. Respir. Cell Mol. Biol.,
January 1, 2007;
36(1):
32 - 42.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Yi, R. Belcastro, S. Shek, D. Luo, M. Post, and A. K. Tanswell
Fibroblast Growth Factor-2 and Receptor-1{alpha}(IIIc) Regulate Postnatal Rat Lung Cell Apoptosis
Am. J. Respir. Crit. Care Med.,
September 1, 2006;
174(5):
581 - 589.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Padela, J. Cabacungan, S. Shek, R. Belcastro, M. Yi, R. P. Jankov, and A. K. Tanswell
Hepatocyte Growth Factor Is Required for Alveologenesis in the Neonatal Rat
Am. J. Respir. Crit. Care Med.,
October 1, 2005;
172(7):
907 - 914.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Ridsdale, M. Roth-Kleiner, F. D'Ovidio, S. Unger, M. Yi, S. Keshavjee, A. K. Tanswell, and M. Post
Surfactant Palmitoylmyristoylphosphatidylcholine Is a Marker for Alveolar Size during Disease
Am. J. Respir. Crit. Care Med.,
July 15, 2005;
172(2):
225 - 232.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Bush, F. Accurso, W. MacNee, S. C. Lazarus, and E. Abraham
Cystic Fibrosis, Pediatrics, Control of Breathing, Pulmonary Physiology and Anatomy, and Surfactant Biology in AJRCCM in 2004
Am. J. Respir. Crit. Care Med.,
March 15, 2005;
171(6):
545 - 553.
[Full Text]
[PDF]
|
|
|
Copyright © 2004 American Thoracic Society
|
|
|
