Tissue injury following inhalation of fine particulate matter and hydrogen peroxide is associated with altered production of inflammatory mediators and antioxidants by alveolar macrophages

Hydrogen peroxide (H₂O₂) is present in the atmosphere at concentrations known to induce cell and tissue damage. However, inhaled H₂O₂ vapor should not reach the lower lung due to its high water solubility. It has been suggested that hygroscopic components of particulate matter (PM) may transport H₂O₂ into the lower lung and induce tissue injury and this was investigated. Ammonium sulfate [(NH₄)₂SO₄] was selected as a model for fine atmospheric PM. Treatment of female Sprague-Dawley rats with (NH₄)₂SO₄ (429 or 215 μg/m³; 0.3-0.4 μm mass median diameter) or H₂0₂ (10, 20, or 100 ppb) alone or in combination for 2 h had no major effect on bronchoalveolar lavage fluid cell number or viability or on protein content or lactate dehydrogenase levels, either immediately or 24 h after exposure, relative to air-exposed rats. However, electron microscopy revealed increased numbers of neutrophils in pulmonary capillaries adhered to the vascular endothelium in rats treated with the combination of (NH₄)₂SO₄ + H₂O₂. Exposure of rats to (NH₄)₂SO₄ + H₂O₂ also resulted in tumor necrosis factor-α (TNF-α) production by alveolar macrophages. This was observed immediately and 24 h after exposure. Immediately after inhalation of (NH₄)₂SO₄ + H₂O₂, a transient increase in production of superoxide anion by alveolar macrophages was observed. In contrast, nitric oxide production by cells from rats exposed to (NH₄)₂SO₄ + H₂O₂ or H₂O₂ alone was decreased, and this persisted for 24 h. Decreases in nitric oxide may be due to superoxide anion-driven formation of peroxynitrite. In this regard, nitrotyrosine, an in vivo marker of peroxynitrite, was detected in lung tissue after exposure of rats to (NH₄)₂SO₄ + H₂O₂ or H₂O₂. We also found that expression of the antioxidant enzyme heme oxygenase-1 by stimulated alveolar macrophages was increased following exposure of rats to (NH₄)₂SO₄ + H₂O₂. Taken together, these studies demonstrate that the biological effects of inhaled fine PM are augmented by H₂O₂. Moreover, tissue injury induced by fine PM may be related to altered production of cytotoxic mediators by alveolar macrophages.