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-(3)H]-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.

Phosphatidylcholine kinetics in neonatal rat lungs and the effects of rhuKGF and betamethasone

“…2). This is consistent with data on newly synthesized PC in adult mouse, rat, and human lung secretions, showing that it initially contributes a lower fraction to surf-PC and that molecular refinement occurs during surfactant recycling (5,8,17). However, whereas in adult organisms such refinement requires up to 24 h, our data show that in neonatal rat lungs refinement occurs within 3 h, indicating a much faster turnover, which is not affected by rhuKGF, betamethasone, or their combination.…”

“…Other PC species are low in surfactant but of high concentration in lung tissue. They contribute to membrane homeostasis or as eicosanoid or docosanoid precursors, e.g., palmitoyl-arachidonoyl-PC (PC16:0/20:4) and palmitoyl-docosahexaenoyl-PC (PC16:0/22:6) (6,7,17).…”

Pulmonary Vascular Endothelial Growth Factor Expression and Disaturated Phospholipid Content in a Chicken Model of Hypoxia-Induced Fetal Growth Restriction

“…In general, these studies demonstrate that hyperoxia stimulates surfactant synthesis [44][45][46] but impairs surfactant function [47] . Moreover, both VEGF and the expression of VEGF receptors are decreased by hyperoxia [48,49] .…”

Gene expression of rat alveolar type II cells during hyperoxia exposure and early recovery

“…These genes were also not identified by a similar DNA microarray analysis of the hyperoxic mouse lungs [14]. However, these genes have been reported to be changed in the lung exposed to hyperoxia [24][25][26][27][28]. The discrepancy may be due to the sensitivity of the detection methods or the absence of the genes on the arrays.…”