McNamara P J, Brouwer K R, Gillespie M N
Biochem Pharmacol. 1986 Feb 15;35(4):621-4. doi: 10.1016/0006-2952(86)90357-6.
Platelet activating factor (PAF; 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent bioactive phospholipid released from platelets, neutrophils, basophils and macrophages that has been proposed as a mediator of anaphylaxis, acute lung injury and other disorders. Specific factors which stabilize PAF and/or regulate PAF activity in body fluids are largely unknown. As part of a general autacoid-serum protein binding screen, the platelet activating factor-alpha-1-acid glycoprotein (PAF-AAG) interaction was indirectly characterized by examining the ability of PAF to displace propranolol from AAG. Both PAF and its deacetylated metabolite (lyso-PAF), at 20 microM, doubled the fraction unbound of propranolol (0.4 microM) from purified human AAG (20 microM). None of the other autacoids that were studied (epinephrine, serotonin, spermidine, putrescine, leu-enkephalin or phenethylamine) exhibited any propranolol displacement activity. Scatchard analysis indicated that PAF competitively displaced propranolol from AAG, causing the apparent affinity constant for propranolol-AAG to decrease from 1.8 X 10(5) M to 6.9 X 10(4) M. PAF behaved qualitatively like chlorpromazine (a documented inhibitor of propranolol binding to AAG), but PAF was less effective at displacing propranolol. The apparent binding to AAG may help stabilize and transport extracellular PAF. Furthermore, the interaction of PAF and AAG suggests that serum AAG, which fluctuates in a number of diseases, may function to regulate PAF activity during acute and chronic disease states.
血小板活化因子（PAF；1-烷基-2-乙酰基-sn-甘油-3-磷酸胆碱）是一种从血小板、中性粒细胞、嗜碱性粒细胞和巨噬细胞释放的强效生物活性磷脂，被认为是过敏反应、急性肺损伤和其他疾病的介质。在体液中稳定PAF和/或调节PAF活性的特定因子在很大程度上尚不清楚。作为一般自体活性物质-血清蛋白结合筛选的一部分，通过检测PAF从α1-酸性糖蛋白（AAG）置换普萘洛尔的能力，间接表征了血小板活化因子-α1-酸性糖蛋白（PAF-AAG）的相互作用。在20微摩尔浓度下，PAF及其脱乙酰化代谢产物（溶血PAF）使普萘洛尔（0.4微摩尔）从纯化的人AAG（20微摩尔）中的未结合分数增加了一倍。所研究的其他自体活性物质（肾上腺素、5-羟色胺、亚精胺、腐胺、亮氨酸脑啡肽或苯乙胺）均未表现出任何普萘洛尔置换活性。Scatchard分析表明，PAF竞争性地从AAG置换普萘洛尔，导致普萘洛尔-AAG的表观亲和常数从1.8×10⁵M降至6.9×10⁴M。PAF在性质上类似于氯丙嗪（一种已证明的普萘洛尔与AAG结合的抑制剂），但PAF置换普萘洛尔的效果较差。与AAG的表观结合可能有助于稳定和转运细胞外PAF。此外，PAF与AAG的相互作用表明，在多种疾病中波动的血清AAG可能在急性和慢性疾病状态下调节PAF活性。
