Oxidized Phospholipids Derived from Ozone-Treated Lung Surfactant Extract Reduce Macrophage and Epithelial Cell Viability

摘要: Ozone is known to be a highly toxic gas present in the urban air which exerts its effect on pulmonary tissue through facile chemical reactions with target molecules airway. One of first barriers encountered by ozone epithelial lining fluid contains surfactant rich glycerophosphocholine lipids. The reaction calf lung extract was found result production 1-palmitoyl-2-(9'-oxo-nonanoyl)-glycerophosphocholine (16:0a/9-al-GPCho) as an expected product ozonolysis abundant unsaturated phospholipids containing fatty acyl groups double bond at carbon-9. This oxidized phospholipid identified biologically active that it reduced elicited macrophage viability necrosis ED(50) 6 microM. Further studies biological activity 16:0a/9-al-GPCho revealed concentrations from 100 200 nM initiated apoptosis epithelial-like A549 cells assessed TUNEL staining, nuclear size, and caspase-3 activation loss indicated reduction mitochondrial dehydrogenase activity. release IL-8, neutrophil chemokine, also stimulated 50-100 16:0a/9-al-GPCho. Exposure low levels (62.5, 125, 250 ppb) for various time periods 2 48 h feedback-regulated exposure chamber resulted dose- time-dependent increase formation measured specific sensitive LC/MS/MS assay. quantity this chain-shortened lipid generated even 125 ppb 2-4 (50-100 nM) consistent mediating effects contact surfactant.