Effects of cerium oxide on rat primary alveolar macrophages.
Ma-JY; Zhao-H; Barger-M; Castranova-V; Ma-JK
Toxicologist 2008 Mar; 102(1):310
Diesel emissions pose health concerns in both environmental and occupational settings. The use of cerium as a fuel-borne catalyst lowers emission of carbonaceous diesel exhaust particles (DEP) and their hydrocarbon content, but results in the emission of ultrafine and fine cerium oxide particles. Due to its nanoparticle size, cerium oxide emission is a potential cause of health concern. Cerium oxide is a thermally stable strong oxidant and is capable of mediating cell-derived nitric oxide levels; thus, it may have a strong effect on alveolar macrophage (AM)-mediated immune/ inflammatory responses. The objective of this study is to characterize the in vitro dose-dependent effects of cerium oxide (1.25 to 50 ug/ml) on rat AM functions in the absence or presence of DEP (50 or 100 ug/ml). AM were isolated from Sprague Dawley rats via bronchoalveolar lavage, cultured with cerium oxide, DEP or their combination for 24 h. Intracellular oxidants and mitochondrial damage of AM were determined using confocal microscopy. The particle-induced cytotoxicity and pro-inflammatory cytokine production by AM were monitored as lactase dehydrogenase (LDH) activity or the level of TNF-alpha and IL-12 in the culture media, respectively. The results show that cerium oxide induced LDH release, significantly blocked resting and LPS-induced nitric oxide and IL-12 production in a dose-dependent manner, but did not induce intracellular superoxide generation, mitochondria damage, or TNF-alpha secretion. Cerium oxide did not affect DEP-induced intracellular ROS or mitochondria damage, but significantly reduced DEP-induced IL-12, but not TNF-alpha, production at rest or in response to LPS. This study shows that direct interaction of cerium oxide with AM results in dose-dependent cellular damage and suppression of macrophage responses to LPS or DEP in the production of nitric oxide and IL-12, thus indicating a potential suppressive effect by cerium oxide on the innate and cell-mediated immunity against respiratory infection.
Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Pulmonary-disorders; Pulmonary-system-disorders; Pulmonary-system; Laboratory-animals; Inhalation-studies; Particulates; Particulate-dust; Environmental-contamination; Environmental-exposure; Environmental-pollution; Occupational-exposure; Occupational-respiratory-disease; Fuels; Fumes; Cell-damage; Cell-metabolism; Cell-transformation; Cellular-reactions; Dose-response; Dosimetry; Diesel-emissions; Diesel-exhausts; Nanotechnology
Mining; Transportation, Warehousing and Utilities
The Toxicologist. Society of Toxicology 47th Annual Meeting and ToxExpo, March 16-20, 2008, Seattle, Washington