Lead disrupts eicosanoid metabolism, macrophage function, and disease resistance in birds

Abstract

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.

Contaminant‐associated alteration of immune function in black‐footed albatross (Phoebastria nigripes), a North Pacific predator

“…Macrophage phagocytosis is one of the first lines of defense against pathogens, and it also is important for antigen presentation and subsequent antibody production. Impaired phagocytic ability increases susceptibility to bacterial and parasitic infection [30], and macrophage phagocytosis has been used to assess immunological response to contaminant exposure in wildlife populations [14,53]. Albatross macrophages from cryopreserved peripheral WBCs responded well in our phagocytosis measurements; 76% of macrophages ingested yeast, with the number of yeast particles that macrophages ingested varying across the categories recorded (% macrophages that ingested 1–2 yeast, 33% ± 5%; 3–4 yeast, 18% ± 5%; 5–10 yeast, 20% ± 7%; gt;10 yeast, 5% ± 4%).…”

Lead Modulation of Macrophages Causes Multiorgan Detrimental Health Effects

“…In vitro experiments with bovine macrophages treated with 10 −4 M Pb showed no impairment in the ability to phagocytize latex beads, but treatment with cadmium and mercury did result in a decrease in phagocytosis by these cells . In contrast, phagocytosis of sheep erythrocytes by peritoneal macrophages isolated from turkey poults, treated with 100 ppm Pb acetate‐trihydrate in their feed, was 50% less than controls and sheep erythrocytes phagocytized per macrophage was 25% less than controls . Impaired phagocytosis of opsonized chicken erythrocytes was observed for rabbit‐derived alveolar macrophages treated with 10 −5 M Pb in culture .…”

Avian Immunotoxicology

“…However, results showed that macrophage function (required to phagocytose circulating Salmonella bacteria) was reduced by lead due to alterations in the phospholipid cell membrane, inducing membrane fragility and loss of integrity. Knowles and Donaldson (1997) also recorded a severalfold increase in secretion of prostaglandins (PGF 2α and PGE 2α ) from macrophages as a result of lead exposure. Prostaglandins secreted by macrophages control the function of other cells in the immune system.…”

“…Antibody production to SRBCs, as measured by the splenic plaque-forming cell assay, also was decreased in lead-dosed birds. On the other hand, upland game birds, including Japanese quail (Coturnix coturnix japonica), turkey poults (Melagris gallaparvo), and chickens (Gallus gallus domesticus), treated with lead acetate in either diets or water, demonstrated little immune responsiveness (Fair & Ricklefs, 2002;Grasman & Scanlon, 1995;Morgan et al, 1975;Lee et al, 2001;Knowles & Donaldson, 1997). Morgan et al (1975) saw no effect on SRBC titers in Japanese quail, and Fair and Ricklefs (2002) also showed no response to challenge with chukar (Alectoris graeca) RBCs or to a nonvirulent strain of Newcastle disease virus.…”

“…This is one of the earliest studies of the potential for natural environmental stress factors, such as dietary deficiency or inadequacy, to impose significant immune system suppression. Knowles and Donaldson (1997) conducted one of the few pathogen challenge studies that have been done in avian immunotoxicology research, inoculating 15-d-old chickens with Salmonella gallinarum and observing them for 14 d to determine if morbidity rates were affected by dietary lead exposure. The course of the infection was similar in treated and untreated birds.…”