Kasperska-Zajac A, Brzoza Z, Rogala B
Chair and Clinical Department of Internal Diseases, Allergology and Clinical Immunology, Medical University of Silesia, Katowice, Poland.
Inflammation. 2008 Apr;31(2):112-20. doi: 10.1007/s10753-007-9056-9. Epub 2008 Jan 12.
Platelet activating factor (PAF) is a potent phospholipid mediator involved in anaphylaxis and chronic inflammatory disorders, including bronchial asthma. PAF is able to act both, directly as a chemotactic factor and indirectly through the release of other inflammatory agents. Apart from its known potent ability to activate platelets, PAF influences other immune and inflammatory cells function involved in asthma, which may be of importance in the pathogenesis of the disease. In addition, PAF administration can mimic some of abnormalities observed in asthma, including bronchoconstriction, bronchial hyper responsiveness, and gas exchange impairment, which may be mediated by leukotrienes acting as secondary mediators of some PAF effects. Therefore, there has been an extensive interest in the role of PAF in human asthma and major efforts have been continued to discover drugs acting thorough inhibition of PAF effects in the disease. Surprisingly, PAF receptor antagonists have not clearly proven their clinical benefits. It may appear that the combined blockage of PAF effects and other mediators involved in asthma is a way to improve clinical efficacy and also an interesting approach to control inflammation in the disease. This review will focus on two main issues: the role of PAF and PAF antagonists in asthma.
血小板活化因子(PAF)是一种强效磷脂介质,参与过敏反应和慢性炎症性疾病,包括支气管哮喘。PAF既能直接作为趋化因子起作用,也能通过释放其他炎症介质间接起作用。除了其已知的激活血小板的强大能力外,PAF还影响哮喘中涉及的其他免疫和炎症细胞功能,这可能在该疾病的发病机制中具有重要意义。此外,给予PAF可模拟哮喘中观察到的一些异常情况,包括支气管收缩、支气管高反应性和气体交换受损,这些可能由作为某些PAF效应二级介质的白三烯介导。因此,人们对PAF在人类哮喘中的作用产生了广泛兴趣,并一直在继续努力寻找通过抑制PAF在该疾病中的作用来发挥作用的药物。令人惊讶的是,PAF受体拮抗剂尚未明确证明其临床益处。似乎联合阻断PAF效应和哮喘中涉及的其他介质是提高临床疗效的一种方法,也是控制该疾病炎症的一种有趣方法。本综述将聚焦于两个主要问题:PAF和PAF拮抗剂在哮喘中的作用。