Eicosanoids and the modulation of glomerular immune injury.
Eicosanoids and the modulation of glomerular immune injury.
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类二十烷酸和肾小球免疫损伤的调节。
DOI：
10.1038/ki.1989.82
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发表时间：
1989
影响因子：
19.6
通讯作者：
E. Lianos
中科院分区：
文献类型：
--
作者：
E. Lianos
出于本综述的目的，肾小球免疫损伤被视为在确定的免疫反应物沉积和相互作用后在肾小球结构水平启动的过程，所述免疫反应物可能激活促炎介质的合成。肾血流动力学紊乱和肾小球毛细血管壁损伤导致蛋白尿是最常见的后遗症。当肾小球损伤是由针对肾小球抗原（结构性或捕获性）或非肾可溶性抗原的特异性抗体沉积引发时，随后的反应可以是炎症或非炎症类型。前者常常与肾小球内补体激活、中性粒细胞和血小板的募集以及致敏单核细胞-巨噬细胞的募集或增强表达相关。在非炎症形式中，毛细血管壁损伤可以单独由抗体沉积介导，或者可能需要补体激活。无论损伤类型如何，免疫反应物沉积在肾小球后，许多促炎介质系统都会被激活。这些系统激活后形成的代谢产物可能介导肾血流动力学和肾小球毛细血管壁的通透性的扰动。此外，它们可能对损伤开始后肾小球结构中招募的内源性肾小球或血源性细胞的功能发挥调节作用。表 1 总结了在各种形式的实验性肾小球肾炎中研究的介质系统。组织培养和分析生物化学等强大研究工具的使用已经产生了大量有关肾组织生物合成能力的信息。肾小球及其各种细胞类型现在被认为是具有自体和促炎作用的脂质化合物合成的活性位点。在具有促炎作用的化合物中，主要重点是类二十烷酸的生物合成和作用。类二十烷酸是花生四烯酸（二十碳四烯酸）和其他含有 20 个碳（eicosa 表示 20）的多不饱和脂肪酸的氧化代谢物。这些多不饱和脂肪酸源自膳食“必需”脂肪酸，并以酯化形式存在于大多数哺乳动物细胞的膜磷酸甘油酯上。关于类二十烷酸的文献呈指数级增长，现在每天大约有 10 篇出版物出现，其中大量与肾脏有关。因此，读者可以参考一些关键参考文献，涉及花生四烯酸在肾细胞磷脂上的分布[11]、花生四烯酸响应细胞表面扰动或受体介导机制的释放[12]、参与花生四烯酸依次转化为前列腺素 (PG)、血栓素 (Tx) [13] 的酶的肾脏区室化、源自细胞色素的代谢物P450 连接的单加氧酶系统 [14] 以及花生四烯酸脂氧合产物（羟基二十碳四烯酸、白三烯和脂氧素）的生物合成和促炎作用 [15, 16]。类二十烷酸表现出令人眼花缭乱且通常差异很大的生物活性谱，并且经常具有相反的生物效应，这可能进一步取决于所研究的物种。冒着过于简单化的风险，本综述将认为花生四烯酸环加氧产物（二烯前列腺素和血栓素）的肾脏作用主要是血管活性的，而花生四烯酸脂氧合产物（羟基二十碳四烯酸和白三烯）的肾脏作用主要是促炎性的。与本综述额外相关的是类二十烷酸在免疫调节中的作用 [17] 及其在调节肾小球细胞功能中的潜在作用，这主要是在系膜细胞中对其收缩特性进行了探索 [18, 19]。
For the purposes of this review, glomerular immune injury is viewed as a process initiated at the level of glomerular structures following deposition and interaction of defined immunologic reactants which may activate the synthesis of proinflammatory mediators. Renal hemodynamic perturbations and glomerular capillary wall injury resulting in proteinuria are the most frequent sequelae. When glomerular injury is initiated by deposition of antibody with specificity against glomerular antigens (structural or trapped) or against non-renal soluble antigens, the ensuing reaction can be of an inflammatory or noninflammatory type. The former is frequently associated with intraglomerular complement activation, recruitment of neutrophils and platelets and recruitment or enhanced expression of sensitized monocytes-macrophages. In noninflammatory forms, capillary wall injury can be mediated by antibody deposition alone or it may require complement activation. Regardless the type of injury, activation of a number of proinflammatory mediator systems has been documented following glomerular deposition of immunologic reactants. The metabolic products formed following activation of these systems may mediate perturbations in renal hemodynamics and in the permeability of the glomerular capillary wall. Moreover, they may play a regulatory role on the function of endogenous glomerular or blood borne cells recruited in glomerular structures following initiation of injury. Table 1 summarizes the mediator systems which have been studied in various forms of experimental glomerulonephritis. The use of powerful investigative tools such as tissue culture and analytical biochemistry has yielded an impressive amount of information regarding the biosynthetic capabilities of renal tissues. The renal glomerulus and its various cell types are now regarded as active sites of synthesis of lipid compounds with autacoid and proinflammatory effects. Of the compounds with proinflammatory effects, major emphasis has been placed on the biosynthesis and role of eicosanoids. Eicosanoids are oxygenated metabolites of arachidonic acid (eicosatetraenoic acid) and other polyunsaturated fatty acids which contain 20 carbons (eicosa indicates 20). These polyunsaturated fatty acids are derived from dietary "essential" fatty acids and are present in esterified form on membrane phosphoglycerides of most mammalian cells. The literature on eicosanoids has been expanding exponentially with approximately 10 publications now appearing daily, a substantial number of which pertain to the kidney. The reader is, therefore, referred to a number of key references regarding the distribution of arachidonate on renal cell phospholipids [11], the release of arachidonate in response to cell-surface perturbations or receptor-mediated mechanisms [12], the renal compartmentalization of enzymes involved in the sequential conversion of arachidonate to prostaglandins (PG), thromboxanes (Tx) [13], the metabolites originating via the cytochrome P450-linked monooxygenase system [14] and the biosynthesis and proinflammatory role of arachidonate lipoxygenation products (hydroxyeicosatetraenoic acids, leukotrienes and lipoxins) [15, 16]. Eicosanoids exhibit a bewildering and often widely differing spectrum of biological activities with frequently opposing biological effects which may further depend on the species studied. At the risk of oversimplifying, this review will regard the renal effects of arachidonate cyclooxy-genation products (dienoic prostaglandins and thromboxanes) as being primarily vasoactive while those of arachidonate lipoxygenation products (hydroxyeicosatetraenoic acids and leukotrienes) as being mainly proinflammatory. Of additional relevance to this review is the role of eicosanoids on immuno-regulation [17] and their potential role in regulating glomerular cell function, which has primarily been explored in mesangial cells with respect to their contractile properties [18, 19].
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实验性膜性肾病中肾小球前列腺素形成增强。
影响因子：
19.6
作者：
Stahl,RA;Adler,S;Baker,PJ;Chen,YP;Pritzl,PM;Couser,WG
通讯作者：
Couser,WG
单侧输尿管结扎改变大鼠肾小球的前列腺素合成。
DOI：
10.1152/ajprenal.1981.241.3.f289
发表时间：
1981
期刊：
The American journal of physiology
影响因子：
--
作者：
Folkert,VW;Schlondorff,D
通讯作者：
Schlondorff,D
膳食鱼油对小鼠狼疮的保护作用。
DOI：
10.1016/s0090-6980(85)80010-1
发表时间：
1985
期刊：
Prostaglandins
影响因子：
--
作者：
Robinson,DR;Prickett,JD;Polisson,R;Steinberg,AD;Levine,L
通讯作者：
Levine,L
血管紧张素 II 对大鼠肾脏磷脂酰肌醇和多磷酸肌醇周转的影响。
DOI：
--
发表时间：
1982
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Benabe,JE;Spry,LA;Morrison,AR
通讯作者：
Morrison,AR
影响因子：
19.6
作者：
M. A. Rahman;S. Emancipator;M. Dunn
通讯作者：
M. A. Rahman;S. Emancipator;M. Dunn