Faculty Bibliography

Cadmium represents a major aquatic pollutant in many parts of the world. Yet, despite the fact that cadmium accumulates in high concentrations in fish tissues, is found in polluted aquatic environments, and is carcinogenic and immunotoxic in a variety of mammalian species, the effects of cadmium on the immune responses of directly exposed aquatic species have not been clearly defined. This study was designed to assess the effects of in vivo cadmium exposure, at a concentration found in contaminated aquatic environments, on the immune defense mechanisms of fish. In this study, no effects were observed upon body weight, lysozyme activity, of cell viability, despite the high concentration of accumulated cadmium in the gills and liver. Furthermore, in the absence of any clinical manifestations or overt toxicity, exposure of rainbow trout to waterborne cadmium at 2 ppb altered macrophage-mediated immune functions, including phagocytosis and free radical production, in a time-dependent manner. Similar immunotoxic effects of cadmium have also been observed in mammals. Although interspecies comparisons between mammalian and fish immune responses are extremely complicated and need to be approached with caution, results from this study suggest the applicability of fish as an additional/alternative animal model for immunotoxicological studies

A symposium entitled Health Risks Associated with Prenatal Metal Exposure was held at the 33rd Annual Meeting of the Society of Toxicology (SOT) in Dallas, Texas. The symposium was cosponsored by the Metals and Reproductive and Developmental Specialty Sections of SOT and was designed to elaborate the health risks associated with in utero exposure to metals commonly found in the workplace and/or ambient environment on the mother and developing offspring. Epidemiological and toxicological evidence that demonstrates the health effects and underlying mechanisms associated with exposure to arsenic (As), lead (Pb), and methyl mercury (MeHg) were discussed, as well as the legal ramifications and personal implications associated with prenatal metal exposure. The following is a summary of each of the individual presentations

Despite the widespread occurrence of acidic sulfur oxides in the ambient environment and their potential risks to human health, effects associated with pulmonary immune defenses have been poorly studied. The current in vivo study was designed to provide some insight into this relatively unexplored area by investigating the impact of inhaled sulfuric acid on immune defense mechanisms critical for maintaining pulmonary resistance against infectious diseases. Results of this study demonstrate that repeated inhalation of sulfuric acid reduces the uptake and intracellular killing of pathogenic bacteria by exposed pulmonary macrophages, and depresses the activity/production of important biological modifiers critical for maintaining pulmonary immunocompetence. These findings have important implications for human health, and may contribute to a better understanding of the possible mechanism(s) underlying the epidemiological evidence which suggests an association between total sulfates in the ambient air and increased incidence of acute bronchitis and lower respiratory illness in school-age children

Rabbit pulmonary macrophages were exposed in vitro to particulate lead oxide (PbO) for periods of up to 72 h and then assayed for the activity of tumor necrosis factor-alpha (TNF alpha) released after stimulation with lipopolysaccharide (LPS). The levels of TNF alpha obtained from PbO-treated cells were decreased in a dose-dependent manner as compared with metal-free control cells for each time point examined. Cells treated simultaneously with both LPS and PbO yielded less monokine than did cells receiving LPS alone. In addition, incubation of cell-free TNF alpha with PbO resulted in a diminution of cytotoxicity directed against TNF alpha-sensitive tumor target cells. Macrophage burdens of PbO particles increased with both the length of incubation and concentration of PbO used; increases in cellular lead burdens were paralleled by reductions in cell viability. Thus, under in vitro conditions, PbO affects the levels of the immunoregulatory monokine TNF alpha and also disrupts its cytotoxic properties after release from activated macrophages

A symposium entitled Immunomodulation by Metals was held at the 32nd Annual Meeting of the Society of Toxicology (SOT) in New Orleans, Louisiana. The symposium was co-sponsored by the Immunotoxicology and Metals Specialty Sections of SOT and was designed to describe the types of adverse immunological reactions which occur in response to environmental and/or occupational exposure to metals. Epidemiological evidence and underlying mechanisms responsible for the observed alterations were also discussed. The following is a summary of each of the individual presentations

Inhaled acids are associated with adverse health effects, a conclusion based largely on studies with particulate-associated acid sulfates. The acidic component of ambient air in some regions, such as California, contains nitric acid (HNO3) vapor, but there is a limited database concerning its biological effects. Furthermore, effects of HNO3 may be modulated by coexposure to other pollutants, such as ozone (O-3). Rabbits were exposed for 4 h/day, 3 days/wk for 4 wk to HNO3 vapor at 0, 50, 150, and 450 mu g/m(3) alone; 0.15 ppm 0(3) alone; or to a mixture of 50 mu g/m(3) HNO3 + 0.15 ppm 0(3). Exposure was followed by assays of biochemical markers in lavage fluid pulmonary macrophage function, and in vitro bronchial responsivity to smooth muscle constrictor challenge. Nitric acid had no effect on viability or numbers of cells recovered, nor on lactate dehydrogenase or total protein in lavage. All acid concentrations reduced both basal levels and stimulated production of superoxide anion by macrophages, while the release/activity of tumor necrosis factor by stimulated macrophages was reduced following exposure to greater than or equal to 150 mu g/m(3) HNO3. Bronchi from rabbits exposed to greater than or equal to 150 mu g/m(3) HNO3 exhibited reduced smooth muscle responsivity in vitro compared to control. Although exposure to the HNO3/O-3 mixture resulted in no interaction for most end points, antagonism was noted for stimulated superoxide production, while synergism was noted for spontaneous superoxide production and bronchial responsivity. Exposure to the mixture resulted in a total abrogation of response to spasmogens in most bronchi examined and a marked attenuation in others. These results indicate that HNO3, when inhaled in vapor phase, may adversely impact upon pulmonary health by affecting target sites throughout the lungs, and that inhalation of an HNO3/O-3 mixture can produce synergistic interaction in affecting some biological parameters