Regulation of the Biosynthesis of Platelet-activating Factor

血小板活化因子(PAF)是多种过敏性和炎症性疾病的重要脂质介质。在本研究中，我们研究了多形核白细胞和巨噬细胞产生PAF的调节机制。乙酰转移酶活性。当细胞受到不同刺激时，乙酰转移酶的活性增加。我们发现，当细胞在37℃升温时，这种酶的活性也会短暂增加，尽管在这种条件下没有观察到PAF的产生。这一结果表明，乙酰转移酶的增加不足以诱导PAF的产生。酮体对PAF产量的影响若以酮体(0.5-5 mm)刺激细胞，则PAF的产生显著增加(2-3倍)。这一观察结果表明，糖尿病患者的PAF合成与正常人相比相当高。这类患者PAF的形成增多可能与临床症状有一定的关系。Lyso-PAF和外源性磷脂酶A_2的作用。加入Lyso-PAF可促进刺激细胞产生PAF。我们还发现，在未经刺激的细胞中加入Lyso-PAF会触发PAF的合成，这表明Lyso-PAF的可用性在诱导PAF的生物合成中是重要的。我们还发现，外源磷脂酶A2的加入会导致PAF合成的增加。值得注意的是，从炎症供体获得的血液和炎性液体中的磷脂酶A_2活性明显较高。如此高的磷脂酶A_2活性可能有利于PAF的形成。嗜酸性粒细胞合成PAF。我们发现，人类低密度嗜酸性粒细胞比正常密度嗜酸性粒细胞产生更多的PAF。

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.