Molecular and functional changes of pulmonary surfactant in response to hyperoxia

Abstract

Surfactant comprises phosphatidylcholine (PC) together with anionic phospholipids, neutral lipids, and surfactant proteins SP-A to-D. Its composition is highly specific, with dipalmitoyl-PC, palmitoyl-myristoyl-PC, and palmitoyl-palmitoleoyl-PC as its predominant PC species, but with low polyunsaturated phospholipids. Changes in pulmonary metabolism and function in response to injuries depend on their duration and whether adaptation can occur. We examined in rats prolonged (7 days) versus acute (2 days) exposure to non-lethal oxygen concentrations (85%) with respect to the composition and metabolism of individual lung phospholipid molecular species. Progressive inflammation, structural alteration, and involvement of type II pneumocytes were confirmed by augmented bromodeoxyuridine incorporation, broadening of alveolar septa, and increased granulocyte, macrophage, SP-A, and SP-D concentrations. Surfactant function was impaired after 2 days, but normalized with duration of hyperoxia, which was attributable to inhibition but not to alteration in SP-B/C concentrations. Phospholipid pool sizes and PC synthesis by lung tissue, as assessed by [methyl-³H]-choline incorporation, were unchanged after 2 days, although after 7 days they were elevated 1.7-fold. By contrast, incorporation of labeled PC into tissue pools of surfactant and lung lavage fluid decreased progressively. Moreover, concentrations of arachidonic acid containing phospholipids were augmented at the expense of saturated palmitoyl-myristoyl-PC and dipalmitoyl-PC. We conclude a persisting impairment in the intracellular trafficking and secretion of newly synthesized PC, accompanied by a progressive increase in alveolar arachidonic acid containing phospholipids in spite of recovery of acutely impaired surfactant function and adaptive increase of overall PC synthesis. Pediatr Pulmonol. 2006, 41:1025–1039.