Pulmonary inflammation due to oxygen toxicity: involvement of chemotactic factors and polymorphonuclear leukocytes.

Although the pathogenesis of pulmonary oxygen toxicity is not fully understood, the fact that increased numbers of polymorphonuclear leukocytes (PMN) are found in the lung and that these increases coincide with the massive endothelial damage raises the possibility that PMN may contribute to lung injury caused by hyperoxia. In order to begin to elucidate a mechanism for this influx of PMN, we measured the chemoattractant activity for PMN of lung lavages of rats exposed to greater than 95% oxygen for various durations. We found that the chemoattractant activity of the lavages of the lungs of rats exposed to hyperoxia for 66 h was markedly increased (9.66 +/- 1.0 times greater) compared with activities in lavages of normoxic control rats. Furthermore, these increases in chemoattractant activity in lung lavages correlated well with increases in the number of PMN (7 times greater than that in normoxic control animals) in the alveolar lavages that occurred after the rats had been exposed to hyperoxia for 66 h. These increases were followed in a few hours by the death of most of the rats (71%). These findings suggested that a close temporal relationship exists between the generation of high concentrations of chemoattractants in lung lavages, PMN influx into lung lavages, and death of rats exposed to hyperoxia. The results supported the possibility that PMN may be involved in the pathogenesis of pulmonary oxygen toxicity.