NEUTROPHILS AND OXYGEN-INDUCED LUNG INJURY - A CASE OF WHEN A FEW IS STILL TOO MANY

The role of neutrophils in acute oxidative lung injury in preterm babi es is presently unclear, with some investigators maintaining they cont ribute to tissue injury while others believe they do not, The aim of t he present study was to determine whether neutropenia, induced by a sp ecific neutrophil antibody, influenced the time course or extent of ox ygen-induced injury of the immature lung, Preterm guinea pigs, deliver ed by caesarean section at 65 days' gestation (term=68 days), were inj ected intraperitoneally with either control serum (CS) or neutrophil a ntiserum (NAS; 200 mu l/100 g body weight) once daily for 5 days, Pups were exposed to 95% oxygen for the first 72 h, acid then allowed to r ecover in 21% oxygen for the subsequent 48 h. Groups of treated animal s were also maintained in 21% oxygen for 5 days, Lungs were examined b y bronchoalveolar lavage (BAL) at 72 h or 120 h. In CS-treated pups, e xposure to 95% oxygen increased both the number of circulating neutrop hils and those recovered by BAT, at both 72 h and 120 h. Protein conce ntration in BAL fluid, an index of lung microvascular permeability, an d BAL elastase and P-glucuronidase activities, indices of neutrophil a ctivation, 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 neutroph ils (72 h, 3.1 vs 0.7 x 10(5)/ml, P<0.05; 120 h, 12.4 vs 3.8 x 10(5)/m l, P<0.05). BAL protein concentration, neutrophil elastase and beta-gl ucuronidase activities in hyperoxia-exposed pups were similar followin g treatment with either CS or NAS, Although the number of circulating neutrophils were markedly depleted and expansion of the alveolar neutr ophil pool was restricted in NAS-treated pups, the neutrophils recruit ed to the lung were activated and could have contributed to the increa se in microvascular permeability in hyperoxia-exposed pups.