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Immunopathologic effects of nickel subsulfide on the primate pulmonary immune system
Abstract:
The effects of nickel subsulfide (Ni3S2) on the pulmonary immune system were evaluated in cynomolgus monkeys that had been previously immunized and repeatedly challenged with sheep red blood cells in specific lung lobes. After instillation of Ni3S2, at a final dose of 0.06 mumol/g lung, in one immunized and one control lobe of each monkey, bronchoalveolar lavage cells were evaluated for alterations in cell number and function. Neither numbers of antibody-forming cells nor natural killer (NK) cell conjugate formation were altered in immunized lobes of nickel-exposed animals regardless of individual lung lobe nickel exposure. Macrophage phagocytic activity was significantly decreased, and target cell killing by conjugate-forming NK cells was increased in all lobes independent of antigen or nickel exposure in all nickel-exposed animals. Histologic sections of nickel-exposed lobes were characterized by mild focal accumulations of macrophages and lymphocytes within the interstitium and alveoli and by perivenular lymphoid infiltration and follicle formation. We conclude that alveolar macrophages are sensitive to the toxic effects of nickel and that local instillation of Ni3S2 in the subhuman primate lung results in suppression of pulmonary alveolar macrophage function accompanied by a secondary increase in NK cell-mediated killing of target cells.
Insights
Nickel subsulfide (Ni3S2) exposure suppressed pulmonary alveolar macrophage function in monkeys. This led to a secondary increase in natural killer (NK) cell activity, impacting the lung immune system.
Area of Science:
- Immunotoxicology
- Pulmonary immunology
- Primate research
Background:
- Nickel subsulfide (Ni3S2) is an industrial compound with known toxicity.
- The effects of Ni3S2 on the primate pulmonary immune system require further elucidation.
- Previous immunization and challenge models provide a framework for assessing localized lung responses.
Purpose of the Study:
- To evaluate the impact of Ni3S2 on the pulmonary immune system in cynomolgus monkeys.
- To assess alterations in bronchoalveolar lavage cell function following Ni3S2 instillation.
- To investigate the relationship between Ni3S2 exposure, macrophage function, and natural killer (NK) cell activity.
Main Methods:
- Cynomolgus monkeys were immunized and challenged with sheep red blood cells in specific lung lobes.
- Ni3S2 was instilled into one immunized and one control lobe per monkey.
- Bronchoalveolar lavage cells were analyzed for cell number and function, including macrophage phagocytosis and NK cell activity.
- Histological examination of lung tissues was performed.
Main Results:
- Macrophage phagocytic activity was significantly decreased in all exposed lobes.
- Target cell killing by NK cells increased in all lobes, independent of nickel or antigen exposure.
- No significant alterations were observed in antibody-forming cells or NK cell conjugate formation in immunized lobes.
- Histology revealed mild inflammatory cell accumulations and lymphoid infiltration in nickel-exposed lobes.
Conclusions:
- Alveolar macrophages are sensitive to the toxic effects of Ni3S2.
- Local Ni3S2 instillation suppresses pulmonary alveolar macrophage function in non-human primates.
- Suppressed macrophage function is accompanied by a secondary increase in NK cell-mediated killing.