Regulation of the Biosynthesis of Platelet-activating Factor

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Platelet-activating factor (PAF) is a potent lipid mediator involved in various allergic and inflammatory diseases. In the present study, we studied the regulatory mechanism of PAF production in polymorphonuclear leukocytes and macrophages.1. Acetyltransferase activity. Acetyltransferase activity was shown to be increased when cells were stimulated with various stimuli. We found that this enzyme activity was also transiently increased when cells were warmed at 37^0C, though PAF production was not observed under such a condition. This result suggest that the increased acetyltransferase is not enough to induce PAF production.2. Effects of ketone bodies on PAF production. If cells were stimulated in the presence of ketone bodies (0.5 mM - 5 mM), the PAF production was markedly increased (2-3 fold). This observation suggests that PAF synthesis in diabetic patients are considerably high compared with normal subjects. The increased PAF formation in such patients may be related to some extent to clinical symptoms.3. Effects of lyso-PAF and exogenous phospholipase A_2. The addition of lyso-PAF augments PAF production in stimulated cells. We also found that the addition of lyso-PAF to unstimulated cells trigger PAF synthesis, suggesting that the availability of lyso-PAF is important in the induction of PAF biosynthesis. we also found that the addition of exogenous phospholipase A_2 leads to the increased PAF synthesis. It is interesting to note that phospholipase A_2 activity in blood and in inflammatory fluids obtained from donors with inflammation are markedly high. Such a high activity of phospholipase A_2 could be favorable for the increased PAF formation.4. PAF synthesis in eosinophils. We found that human hypodense eosinophils produce larger amounts of PAF than normodense eosinophils.