Comparison of Pulmonary Neutrophils in the Adult and Neonatal Rat after Hyperoxia

Abstract

The mechanisms of the increased tolerance to hyperoxia of neonatal animals of many species is incompletely understood. To investigate the etiology of this difference we compared neutrophi1 entry into the lungs of neonatal and adult rats after hyperoxic exposure. Adult rats were studied after exposure to 298% 0, for 60 h and neonatal rats after 3 and 7 d. Neonatal survival was prolonged compared with that reported for adult rats (77% after 7 d of exposure). In adult rats, there were significant increases in pulmonary neutrophils after 60 h of 0, exposure. In neonatal rats, these changes were not evident after 72 h of exposure, but pulmonary neutrophils increased after 7 d of hyperoxia. Before mortality, pulmonary neutrophils were distributed differently in the age groups. After 7 d of 0, exposure in the neonates, total neutrophil counts in lung tissue (21.92 1 7.29 per cm2 grid) andThe mechanisms of prolonged neonatal tolerance to hyperoxia, which has been noted in the young of many species (1-3), are not completely understood. Species such as the rat, mouse, and rabbit, whose neonates exhibit tolerance, also demonstrate greater induction of antioxidant enzymes than adults in response to hyperoxia (1, 3). This enzyme increase is not seen in the guinea pig and hamster, whose neonates do not exhibit tolerance (1, 3). However, tolerance could also be related to a lower risk of hyperoxic cellular injury to the neonatal lung as a result of diminished oxygen free radical release, a hypothesis which has not been extensively investigated. Ischiropoulos et al. (4) showed lower subcellular superoxide generating capacity in response to 0, in neonatal rats compared with adults. Although the rate of generation of cellular reactive 0, species increases after hyperoxia (5,6), neutrophil accumulation would be expected to augment the total oxidant load presented to pulmonary cells. Neutrophils accumulate in the lung after hyperoxic exposure (7, 8), where they may produce localized damage due to release of toxic oxygen radicals, arachidonic acid metabolites and proteases (9, 10). lung myeloperoxidase (0.085 -t 0.02 Ulmg protein) remained significantly lower than in adults after 60 h of 0, exposure (41.44 5 9.08 per cm2 grid and 0.411 -t 0.085 Ulmg protein, respectively). However, in histologic specimens, 0,-exposed neonates had higher percentages of neutrophils free in the alveolar air space than did adults, corresponding to a trend toward higher neutrophil counts in bronchoalveolar lavage fluid in the neonates. It appears that, in addition to delay in neutrophil influx into the lung, neonatal rats have lowered retention of neutrophils to the alveolar tissue. It is controversial whether neutrophil-mediated responses are necessary for production of acute hyperoxic lung injury. Data implicating neutrophils in the etiology of acute pulmonary oxygen toxicity include neutrophil depletion studies in rabbits, mice, and sheep (1 1-13) and studies correlating diminished inflammatory response with protection from 0,-induced lung injury in...

CXCR2 Is Critical to Hyperoxia-Induced Lung Injury

“…Our findings of a significant increase in neutrophil infiltration in hyperoxia-exposed mice complement and extend the conclusions of other studies that found that high concentrations of oxygen led to the release of reactive oxygen species that promoted neutrophil infiltration into the lung (41,42). Lungs taken from multiple species after 24 h of hyperoxia, when studied by electron microscopy, demonstrate a diffuse infiltration of activated neutrophils (43). In addition, increases in P-selectin and up-regulation in ICAM-1, a ligand for neutrophil ␤ 2 integrins, have been demonstrated early in the course of hyperoxia exposure, lending further evidence for a neutrophil-mediated injury (44 -47).…”

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