Touqui L, Herpin-Richard N, Gene R M, Jullian E, Aljabi D, Hamberger C, Vargaftig B B, Dessange J F
Unité de Pharmacologie Cellulaire, Unité Associée Institut Pasteur-INSERM no. 285, Paris, France.
J Allergy Clin Immunol. 1994 Jul;94(1):109-19. doi: 10.1016/0091-6749(94)90077-9.
Platelet activating factor (PAF), a proinflammatory mediator synthesized through a phospholipase A2 (PLA2)-dependent reaction, is hydrolyzed into its inactive metabolite, lyso-PAF, by a specific acetylhydrolase. Previous studies have shown that allergen challenge of patients with allergic rhinitis leads to an increase of the concentrations of lyso-PAF in nasal lavage fluid (NLF), whereas PAF is detected only marginally. PAF-hydrolyzing enzymes are expected to be released on allergenic challenge, to account for the reduced concentrations of PAF in NLF. Here, we show that allergen challenge of patients with allergic rhinitis induces an increase of acetylhydrolase-like activity in NLF, which peaks within 10 minutes and returns to basal values 1 hour later. Acetylhydrolase hydrolyzed exogenous PAF with a complete loss of its ability to induce platelet aggregation. Allergen challenge also led to a parallel release of a PLA2 in nasal fluids. This enzyme preferentially hydrolyzes negatively charged phospholipids (phosphatidic acid monomethyl ester and phosphatidylgylcerol) versus phosphatidylcholine. More interestingly, the hydrolysis of phosphatidic acid monomethyl ester and phosphatidylglycerol by NLF was completely abolished by the addition of ethylenediaminetetraacetic acid which had no effect on the hydrolysis of PAF, indicating that the PLA2 secreted in nasal fluids is not involved in the degradation of PAF. Finally, our results show that allergen-induced increase in the concentrations of lyso-PAF and prostaglandin D2 occurred with a kinetic similar to that of tosyl-L-arginine-methyl-ester esterase, suggesting that mast cells are implicated in this process. Although no direct relationship was demonstrated between the absence of PAF and the increase of acetylhydrolase levels in NLF, we suggest a potential role for this enzyme in the inactivation of PAF if the latter is released in the nasal lumen.
血小板活化因子（PAF）是一种通过磷脂酶A2（PLA2）依赖性反应合成的促炎介质，可被一种特异性乙酰水解酶水解为其无活性代谢产物溶血PAF。先前的研究表明，变应原激发过敏性鼻炎患者会导致鼻灌洗液（NLF）中溶血PAF浓度升高，而PAF仅能被少量检测到。预计变应原激发时会释放PAF水解酶，以解释NLF中PAF浓度降低的原因。在此，我们表明变应原激发过敏性鼻炎患者会导致NLF中乙酰水解酶样活性增加，该活性在10分钟内达到峰值，并在1小时后恢复到基础值。乙酰水解酶水解外源性PAF，使其诱导血小板聚集的能力完全丧失。变应原激发还导致鼻液中PLA2平行释放。该酶优先水解带负电荷的磷脂（磷脂酸单甲酯和磷脂酰甘油）而非磷脂酰胆碱。更有趣的是，添加乙二胺四乙酸可完全消除NLF对磷脂酸单甲酯和磷脂酰甘油的水解，而这对PAF的水解没有影响，表明鼻液中分泌的PLA2不参与PAF的降解。最后，我们的结果表明，变应原诱导的溶血PAF和前列腺素D2浓度增加的动力学与甲苯磺酰-L-精氨酸甲酯酶相似，提示肥大细胞参与了这一过程。尽管未证明NLF中PAF的缺失与乙酰水解酶水平升高之间存在直接关系，但我们认为如果PAF释放到鼻腔中，该酶在PAF失活中可能具有潜在作用。
