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SYNTHETIC COPPER-CONTAINING PARTICLES ENHANCE ALLERGIC AIRWAY RESPONSES IN MICE
Impact/Purpose:
This mechanistic work will help support epidemiological findings of adverse health effects of exposure to PM by identifying and characterizing processes that are plausibly affected by PM and whose disruption may lead to disease.
Description:
Respiratory morbidity and mortality associated with increases in ambient levels of particulate matter (PM) may be dependent on particle elemental composition. Particle-associated metals such as copper may catalyze formation of reactive oxygen species leading to inflammation and lung injury. We studied the ability of chemically defined synthetic particles to enhance allergic inflammation and airway hyperresponsiveness in ovalbumin (OVA)-allergic mice. Particles (< 2 mm) were synthesized with a base of 50% carbon, 15% NH4Cl, and 30% Na2SO4. Control carbon (C) particles contained an extra 5% carbon, while carbon-zinc (CZn) or carbon-copper (CCu) particles contained 5% zinc sulfate or copper sulfate [2.0% Zn(II) or Cu(II) metal; 0.31 mmol/gm particle]. Female BALB/cJ mice were sensitized i.p. with OVA in aluminum hydroxide adjuvant or were administered adjuvant only; all mice were challenged with OVA aerosol 14 or 15 d later. One hour after challenge mice were intratracheally instilled with saline, C, CZn, or CCu in saline vehicle (2 mg/kg; ~40 mg). Both nonallergic and allergic CCu-exposed mice were hyperresponsive to methacholine aerosol challenge (Buxco; 4-32 mg/ml) 1 day (~4-fold increase) and 8 days (~2-fold increase) after exposure compared with all other groups. Bronchoalveolar lavage (BAL) fluid eosinophils, neutrophils, lactate dehydrogenase, protein, albumin, N-acetyl-b-D-glucosaminidase, interleukins-4, -5, -13, interferon-g, and tumor necrosis factor-a were all significantly increased in CCu-exposed mice compared with saline, C, or CZn-exposed groups. These data show that PM-associated copper enhances allergic inflammation and airway hyperresponsiveness in mice, and are consistent with recent studies relating toxicological effects with epidemiological findings of health effects of PM containing high concentrations of copper.