Inhalation of particulate lead oxide disrupts pulmonary macrophage-mediated functions important for host defense and tumor surveillance in the lung.
Lead, an immunomodulator and potential human carcinogen, is a major airborne pollutant in industrial environments which poses a serious threat to human health. Despite the wide-spread occurrence of respirable lead particles in the air, and the potential human health risks, effects associated with inhalation of particulate lead on the the lung have been poorly studied. This study was performed to determine whether inhalation of particulate lead oxide (PbO), at a concentration below the currently acceptable air lead standard for occupational exposure, disrupts macrophage (M phi) functions important for maintaining pulmonary immunocompetence. These functions include phagocytosis, production of reactive oxygen intermediates, and the biological activity of tumor necrosis factor-alpha (TNF-alpha). Rabbits exposed to PbO at 30 micrograms/m3 for 4 days (3 hr/day) were sacrificed and their lungs lavaged immediately, 24 hr, and 72 hr after the final exposure. Lactate dehydrogenase (a marker of lung cell damage) and lysozyme activity (a marker of lysosome permeability), measured in the lavage fluid, were significantly increased 24 and 72 hr after exposure. PbO produced neutrophil infiltration nor effects on M phi viability or total numbers. Effects on M phi functions were as follows. Phagocytic uptake of latex particles was reduced with increasing post-exposure time reaching a maximum inhibition at 72 hr. Inhalation of PbO enhanced hydrogen peroxide (H2O2) and superoxide anion radical (O2-) production in a time-dependent manner; effects on H2O2 began at 24 hr and were persistent up to 72 hr. Effects on TNF-alpha release/activity appeared earliest and were persistent up to 72 hr. Immediately and 24 hr after exposure, lipopolysaccharide-stimulated activity of TNF-alpha was depressed by 62 and 50%, respectively; after 72 hr, TNF-alpha release was significantly enhanced compared to control levels. Results demonstrate that the lung is a sensitive target for the toxic effects of inhaled lead. This study provides the first evidence that inhalation of particulate lead, at an occupationally relevant concentration, and in the absence of elevated blood lead levels, alters pulmonary M phi functions critical for lung defense against inhaled antigens. Our findings may have important implications for human health and should be considered when evaluating the health risks associated with inhaled lead.
Institute of Environmental Medicine, New York University Medical Center, New York 10016.
J T
JT
Zelikoff
E
E
Parsons
R B
RB
Schlesinger
D000393:Air Pollutants / Q000009:adverse effects*; D000818:Animals; D006861:Hydrogen Peroxide / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007854:Lead / Q000009:adverse effects* / Q000032:analysis; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009113:Muramidase / Q000378:metabolism; D010087:Oxides / Q000009:adverse effects*; D010587:Phagocytosis / Q000187:drug effects*; D011817:Rabbits; D013047:Specific Pathogen-Free Organisms; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000393:Air Pollutants; D010087:Oxides; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D007854:Lead; C047365:lead oxide; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D009113:Muramidase