Platelet-activating factor (PAF)-acetylhydrolase and PAF-like compounds in the lung: effects of hyperoxia.

Platelet-activating factor (PAF)-acetylhydrolase is the enzyme modulating in tissues and biological fluids the concentration of the proinflammatory factors PAF and PAF-like oxidation products of phospholipids (PAF-like compounds). We investigated whether there is a relation between PAF-acetylhydrolase activity and the concentration of PAF-like compounds in bronchoalveolar lavage (BAL). We found that alveolar type II cells are an additional source of PAF-acetylhydrolase in BAL beside macrophages. Secretion of PAF-acetylhydrolase was stimulated by phorbol ester in alveolar type II cells but not in macrophages. Studies in BAL suggested that secreted PAF-acetylhydrolase was bound to alveolar surfactant. Exposure of rats to high oxygen concentration reduced the activity of PAF-acetylhydrolase in BAL and macrophages, but not in plasma or alveolar type II cells. In contrast, hyperoxia increased the concentration of PAF-like-compounds, lipid hydroperoxides and malonedialdehyde in plasma but not in BAL. Therefore, we conclude that neither the oxidant-induced decrease of the PAF-acetylhydrolase activity nor the direct peroxidation of surfactant lipids in the alveoli provide a likely mechanism for hyperoxia-induced lung injury. Instead, lung injury is apparently caused by lipid peroxidation in plasma rather than by high oxygen pressure in the alveoli.