Lead disrupts eicosanoid metabolism, macrophage function, and disease resistance in birds.
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.
Knowles
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SO
Department of Toxicology, North Carolina State University, Raleigh 27695-7608, USA.
Donaldson
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WE
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002478:Cells, Cultured; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004198:Disease Susceptibility / Q000139:chemically induced* / Q000276:immunology; D015777:Eicosanoids / Q000378:metabolism*; D007113:Immunity, Innate / Q000187:drug effects; D007854:Lead / Q000008:administration & dosage / Q000633:toxicity*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009942:Organometallic Compounds / Q000008:administration & dosage; D010587:Phagocytosis / Q000187:drug effects; D012481:Salmonella Infections, Animal / Q000276:immunology; D018805:Sepsis / Q000276:immunology; D013929:Thromboxane B2 / Q000378:metabolism; D014422:Turkeys
D015777:Eicosanoids; D008070:Lipopolysaccharides; D009942:Organometallic Compounds; D016718:Arachidonic Acid; D007854:Lead; D013929:Thromboxane B2; D015237:Dinoprost; D015232:Dinoprostone; C008261:lead acetate