Knowles S O, Donaldson W E
Department of Toxicology, North Carolina State University, Raleigh 27695-7608, USA.
Biol Trace Elem Res. 1997 Oct-Nov;60(1-2):13-26. doi: 10.1007/BF02783306.
Lead (Pb) affects elements of humoral and cell-mediated immunity, and diminishes host resistance to infectious disease. Evidence is presented supporting a hypothesis of Pb-induced immunosuppression stemming from altered fatty acid metabolism, and mediated by eicosanoids and macrophages (MO). Chronic Pb exposure increases the proportion of arachidonate (ArA) among fatty acids in lipid from avian tissues, and this change provides precursors for eicosanoids, the oxygenated derivatives of ArA that mediate MO acute inflammatory response. In the current study, we showed that the concentration of ArA in phospholipids of MO elicited from turkey poults fed 100 ppm dietary Pb acetate was twice that of controls. In vitro production of eicosanoids by these MO was substantially increased, and this effect was most pronounced following lipopolysaccharide stimulation: prostaglandin F2 alpha was increased 11-fold, thromboxane B2 increased threefold, and prostaglandin E2 increased by 1.5 times. In vitro phagocytic potential of these MO was suppressed, such that the percentage of MO engulfing sheep red blood cell (RBC) targets was reduced to half that of control MO. In vivo susceptibility of Pb-treated and control birds to Gram-negative bacteria challenge was also evaluated. The morbidity of chicks inoculated with Salmonella gallinarum and fed either control or 200 ppm Pb acetate-supplemented diets was similar, except early in the course of the disease when mortality among Pb-treated birds was marginally greater. In these studies, effects of Pb that could influence immunological homeostasis were demonstrated for MO metabolism of ArA, for production of eicosanoids, and for phagocytosis. There was also the suggestion that these in vitro indices of immune function are related to in vivo disease resistance.
铅（Pb）会影响体液免疫和细胞介导免疫的元素，并降低宿主对传染病的抵抗力。本文提供的证据支持了一种假设，即铅诱导的免疫抑制源于脂肪酸代谢改变，并由类花生酸和巨噬细胞（MO）介导。长期接触铅会增加禽类组织脂质中脂肪酸中花生四烯酸（ArA）的比例，这种变化为类花生酸提供了前体，类花生酸是介导MO急性炎症反应的ArA氧化衍生物。在当前的研究中，我们发现，喂食100 ppm醋酸铅日粮的火鸡雏鸡所产生的MO的磷脂中ArA的浓度是对照组的两倍。这些MO在体外产生的类花生酸大幅增加，这种效应在脂多糖刺激后最为明显：前列腺素F2α增加了11倍，血栓素B2增加了3倍，前列腺素E2增加了1.5倍。这些MO的体外吞噬潜力受到抑制，因此吞噬绵羊红细胞（RBC）靶标的MO百分比降至对照MO的一半。还评估了铅处理组和对照组鸟类在体内对革兰氏阴性菌攻击的易感性。接种鸡沙门氏菌并喂食对照或添加200 ppm醋酸铅日粮的雏鸡的发病率相似，只是在疾病早期，铅处理组的死亡率略高。在这些研究中，证明了铅对MO的ArA代谢、类花生酸的产生和吞噬作用等可能影响免疫稳态的效应。也有迹象表明，这些免疫功能的体外指标与体内抗病能力有关。
