Upton Julia E M, Grunebaum Eyal, Sussman Gordon, Vadas Peter
Division of Immunology and Allergy, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
Biofactors. 2022 Nov;48(6):1189-1202. doi: 10.1002/biof.1883. Epub 2022 Aug 27.
Platelet-activating factor (PAF) is a phospholipid-derived mediator with an established role in multiple inflammatory states. PAF is synthesized and secreted by multiple cell types and is then rapidly hydrolyzed and degraded to an inactive metabolite, lyso-PAF, by the enzyme PAF acetylhydrolase. In addition to its role in platelet aggregation and activation, PAF contributes to allergic and nonallergic inflammatory diseases such as anaphylaxis, sepsis, cardiovascular disease, neurological disease, and malignancy as demonstrated in multiple animal models and, increasingly, in human disease states. Recent research has demonstrated the importance of the PAF pathway in multiple conditions including the prediction of severe pediatric anaphylaxis, effects on blood-brain barrier permeability, effects on reproduction, ocular diseases, and further understanding of its role in cardiovascular risk. Investigation of PAF as both a biomarker and a therapeutic target continues because of the need for directed management of inflammation. Collectively, studies have shown that therapies focused on the PAF pathway have the potential to provide targeted and effective treatments for multiple inflammatory conditions.
血小板活化因子(PAF)是一种磷脂衍生介质,在多种炎症状态中发挥着既定作用。PAF由多种细胞类型合成和分泌,然后被PAF乙酰水解酶迅速水解并降解为无活性代谢物溶血PAF。除了在血小板聚集和激活中的作用外,PAF还参与过敏性和非过敏性炎症性疾病,如过敏反应、败血症、心血管疾病、神经疾病和恶性肿瘤,这在多个动物模型中得到了证实,并且在人类疾病状态中也越来越多地得到证实。最近的研究表明,PAF途径在多种情况下都很重要,包括预测严重小儿过敏反应、对血脑屏障通透性的影响、对生殖的影响、眼部疾病,以及进一步了解其在心血管风险中的作用。由于需要对炎症进行定向管理,因此对PAF作为生物标志物和治疗靶点的研究仍在继续。总体而言,研究表明,针对PAF途径的疗法有可能为多种炎症性疾病提供有针对性的有效治疗。