The Role of Platelet‐Activating Factor in Cerebral Ischemia and Related Disorders
The Role of Platelet‐Activating Factor in Cerebral Ischemia and Related Disorders
复制标题
血小板激活因子在脑缺血及相关疾病中的作用
DOI：
10.1111/j.1749-6632.1989.tb22617.x
复制
发表时间：
1989
影响因子：
5.2
通讯作者：
N. G. Bazan
中科院分区：
文献类型：
--
作者：
P. Braquet;B. Spinnewyn;C. Demerlé;D. Hosford;V. Marcheselli;M J Rossowska;N. G. Bazan
血小板活化因子（PAF）是一种有效的类自身介质，涉及多种人类疾病，包括哮喘、休克、心脏和全身过敏反应、溃疡、牛皮癣、免疫和肾脏疾病以及各种炎症（文献1,2）。也有大量证据表明PAF参与中枢神经系统（CNS）功能和缺血性疾病（文献1）。烷基磷脂最初是从抗原刺激的兔嗜碱性粒细胞中分离出来的，结构特征是1- o-烷基-2(R)-乙酰-甘油-3-磷酸胆碱，现在已知由多种细胞类型产生并作用于这些细胞类型，包括中性粒细胞、嗜酸性粒细胞、单核细胞、巨噬细胞、血小板和内皮细胞（参见文献1,2）。在细胞刺激下合成磷酸腺苷通常被认为涉及磷脂酶A2 （PLA2）对前体分子1-烷基-2-酰基-甘油- 3-磷酸胆碱（1-烷基-2-酰基- gpc）的去酰化，随后通过特定的乙酰转移酶将2-lyso-PAF乙酰化为活性PAF分子（参见文献1,3）。对PAF的病理生理作用的研究已经被各种合成和天然化合物所促进，这些化合物可以特异性地拮抗这种介质。合成拮抗剂（参见文献4）-例如CV-6209（武田），SRI 63- 444 1（山德士）和Ro 19-3704（霍夫曼-拉罗彻）-主要来源于PAF框架；尽管结构无关的R P 55270 （RhonePoulenc）、WEB 2086和WEB 2170（勃林格）也是有效的抑制剂。最大的一类特异性PAF拮抗剂来自天然来源，包括：(i)银杏内酯（即bn52021； Institut Henri Beaufour），来自银杏叶的独特的20碳笼状分子（见文献5）；（ii）从Piper futokadsurae中分离的木脂素，如kadsurenone和相关的合成呋喃骨架l - 652,731和L-659,989 (Merck)；（iii）由各种真菌和细菌产生的一些胶质毒素相关化合物（如FR-900452； fusjawa）。在这篇综述中，我们将考虑PAF的作用和上述一些拮抗剂在缺血性疾病中的作用。在脑缺血开始时，磷脂酶A和C的激活导致游离脂肪酸和二酰基甘油的积累由于游离多不饱和脂肪酸是扩大的游离脂肪酸池的主要成分，因此
Platelet-activating factor (PAF) is a potent autacoid mediator implicated in a diverse range of human pathologies, including asthma, shock, cardiac and systemic anaphylaxis, ulceration, psoriasis, immune and renal disorders, and a variety of inflammatory conditions (reviewed i n References 1,2). There is also considerable evidence suggesting the involvement of PAF in central nervous system (CNS) functions and ischemic diseases (reviewed in Reference 1). Originally isolated from antigen-stimulated rabbit basophils and characterized structurally is 1-O-alkyl-2(R)-acetyl-glycero-3-phosphocholine, the alkyl phospholipid is now known to be produced by, and act on, a variety of cell types, including neutrophils, eosinophils, monocytes, macrophages, platelets, and endothelial cells (reviewed in References 1,2). The synthesis of P A F upon cell stimulation is generally accepted as involving a deacylation of the precursor molecule, 1 -alkyl-2-acyl-glycero3-phosphocholine (1-alkyl-2-acyl-GPC) by a phospholipase A2 (PLA2) and a subsequent acetylation of the 2-lyso-PAF to the active PAF molecule by a specific acetyltransferase (reviewed in References 1,3). Studies on the pathophysiological role of PAF have been facilitated by a variety of synthetic and natural compounds that can specifically antagonize the mediator. Synthetic antagonists (reviewed in Reference 4)-for example, CV-6209 (Takeda), SRI 63-44 1 (Sandoz), and Ro 19-3704 (Hoffman-LaRoche)-are derived mainly from the PAF framcwork; although the structurally unrelated R P 55270 (RhonePoulenc), WEB 2086, and WEB 2170 (Boehringer) are also potent inhibitors. The largest group of specific PAF antagonists derive from natural sources and comprise: (i) the ginkgolides (i.e., BN 52021 ; Institut Henri Beaufour), unique twenty-carbon cage molecules from the leaves of Ginkgo biloba (reviewed in Reference 5); (ii) lignans such as kadsurenone isolated from Piper futokadsurae and the related synthetic furanoid frameworks L-652,73 1 and L-659,989 (Merck); and (iii) some gliotoxin-related compounds (i.e., FR-900452; Fusijawa) produced by various fungi and bacteria. In this review we will consider the role of PAF and the effects of some of the above antagonists in ischemic conditions. At the onset of brain ischemia, the activation of phospholipases A and C leads to the accumulation of free fatty acids and diacylglycerols.6 Since free polyunsaturated fatty acids are the predominant components of the enlarged free fatty acid pool,' the
人类中性粒细胞和嗜酸性粒细胞中血小板激活因子（1-烷基-2-乙酰基-sn-甘油-3-磷酸胆碱）代谢酶的活性以及钙离子载体的作用。
DOI：
10.1016/0006-291x(82)90928-7
发表时间：
1982
影响因子：
3.1
作者：
Lee,TC;Malone,B;Wasserman,SI;Fitzgerald,V;Snyder,F
通讯作者：
Snyder,F
人内皮细胞是血小板激活因子的靶标。
DOI：
--
发表时间：
1987
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bussolino,F;Camussi,G;Aglietta,M;Braquet,P;Bosia,A;Pescarmona,G;Sanavio,F;D'Urso,N;Marchisio,PC
通讯作者：
Marchisio,PC
影响因子：
8.3
作者：
SHAH, AB;BEAMER, N;COULL, BM
通讯作者：
COULL, BM