title: Neutrophils and oxygen-induced lung injury: a case of when a few is still too many.
abstract: The role of neutrophils in acute oxidative lung injury in preterm babies is presently unclear, with some investigators maintaining they contribute to tissue injury while others believe they do not. The aim of the present study was to determine whether neutropenia, induced by a specific neutrophil antibody, influenced the time course or extent of oxygen-induced injury of the immature lung. Preterm guinea pigs, delivered by caesarean section at 65 days' gestation (term=68 days), were injected intraperitoneally with either control serum (CS) or neutrophil antiserum (NAS; 200 μl/100 g body weight) once daily for 5 days. Pups were exposed to 95% oxygen for the first 72 h, and then allowed to recover in 21% oxygen for the subsequent 48 h. Groups of treated animals were also maintained in 21% oxygen for 5 days. Lungs were examined by bronchoalveolar lavage (BAL) at 72 h or 120 h. In CS-treated pups, exposure to 95% oxygen increased both the number of circulating neutrophils and those recovered by BAL at both 72 h and 120 h. Protein concentration in BAL fluid, an index of lung microvascular permeability, and BAL elastase and β-glucuronidase activities, indices of neutrophil activation, were significantly increased in pups exposed to 95% oxygen. Pups exposed to 95% oxygen and treated with NAS showed a decrease in numbers of circulating neutrophils (72 h, 9.53 vs 0.66 x 10(5)/ml, P<0.0005; 120 h, 4.9 vs 0.08 x 10(5)/ml, P<0.0005) and BAL fluid neutrophils (72 h, 3.1 vs 0.7 x 10(5)/ml, P<0.05; 120 h, 12.4 vs 3.8 x 10(5)/ml, P<0.05). BAL protein concentration, neutrophil elastase and β-glucuronidase activities in hyperoxia-exposed pups were similar following treatment with either CS or NAS. Although the number of circulating neutrophils were markedly depleted and expansion of the alveolar neutrophil pool was restricted in NAS-treated pups, the neutrophils recruited to the lung were activated and could have contributed to the increase in microvascular permeability in hyperoxia-exposed pups.
authors.affiliation: a Cardiovascular Research, The Rayne Institute, St Thomas' Hospital , London , UK , and Departments of Child Health and Human Nutrition , University of Southampton , Southampton , UK.
authors.forename: F J
authors.initials: FJ
authors.lastname: Kelly
authors.affiliation: a Cardiovascular Research, The Rayne Institute, St Thomas' Hospital , London , UK , and Departments of Child Health and Human Nutrition , University of Southampton , Southampton , UK.
authors.forename: A D
authors.initials: AD
authors.lastname: Postle
authors.affiliation: a Cardiovascular Research, The Rayne Institute, St Thomas' Hospital , London , UK , and Departments of Child Health and Human Nutrition , University of Southampton , Southampton , UK.
authors.forename: G J
authors.initials: GJ
authors.lastname: Phillips