Inhaled nitric oxide decreases leukocyte trafficking in the neonatal mouse lung during exposure to >95% oxygen.
Chronic lung injury in the neonate is termed bronchopulmonary dysplasia (BPD). These patients generally require supplemental oxygen therapy, and hyperoxia has been implicated in the pathogenesis of BPD. The concomitant use of oxygen and inhaled NO (iNO) may result in the generation of reactive nitrogen species or may have an anti-inflammatory effect in the neonatal lung. We tested the hypothesis that exposure to >95% O2 in neonatal mice would increase trafficking of leukocytes into the lung and that the addition of iNO to >95% O2 would decrease this leukocyte trafficking. Hyperoxia resulted in fewer alveoli, increased presence of neutrophils and macrophages, and decreased number of mast cells within the lung parenchyma. Adding iNO to hyperoxia prevented the hyperoxia-induced changes and resulted in the numbers of alveoli, neutrophils, macrophages, and mast cells approximating those found in controls (room air exposure). Intercellular adhesion molecule (ICAM) and monocyte chemotactic protein-1 (MCP-1), two factors responsible for leukocyte recruitment, were up-regulated by hyperoxic exposure, but the addition of iNO to the hyperoxic exposure prevented the hyperoxia-induced up-regulation of ICAM and MCP-1. These data demonstrate that iNO alters the hyperoxia-induced recruitment of leukocytes into the lung.
Rose
Melissa J
MJ
Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio 43205, USA.
Stenger
Michael R
MR
Joshi
Mandar S
MS
Welty
Stephen E
SE
Bauer
John Anthony
JA
Nelin
Leif D
LD
D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D018932:Chemokine CCL2 / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004195:Disease Models, Animal; D018496:Hyperoxia / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects; D009569:Nitric Oxide / Q000008:administration & dosage*; D010100:Oxygen; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D010100:Oxygen