Soluble and Insoluble Air Particle Fractions Induce Differential Production of Tumor Necrosis Factor Α in Rat Lung

Abstract

Altered cytokine production in the lung follows the deposition of urban air particles. The present study was designed to measure changes in tumor necrosis factoralpha (TNFalpha) and endothelin-1 (ET-1) levels in rat lung after instilling various fractions of the dust EHC-93, while in vitro, alveolar macrophages (AMs) and type 2 epithelial cells were studied to determine relative production of these molecules in response to the same particles. Whole dust and its soluble and leached components were instilled into rat lung and the animals were killed at intervals to 2 weeks; they received tritiated thymidine by intraperitoneal injection 1 hour before death. All samples induced some inflammation, with the highest cellular efflux being found by bronchoalveolar lavage 1 day after leached particles. Lung injury, illustrated by protein levels in lavage fluid, was maximal after instilling the soluble fraction and subsequently epithelial regeneration was also maximal in this group. TNFalpha levels were highest after instilling whole dust or its leached fraction at 4 hours and 1 day, and cell culture studies indicated a predominant AM source for this cytokine. ET-1 levels were also increased in BAL from 4 hours to 3 days and were mostly associated with the instillation of leached particles. The results demonstrate that the rapid production/release of TNFalpha and ET-1 after particle deposition is largely due to the insoluble particulate fraction. There appears to be a differential response to whole dust where the soluble components cause some inflammation and epithelial cell necrosis, whereas the leached particles are more likely to react with macrophages to induce the production of proinflammatory cytokines such as TNFalpha.

Dose and Time Dependency of Inflammatory Responses in the Mouse Lung to Urban Air Coarse, Fine, and Ultrafine Particles From Six European Cities

“…We observed that the increases in BALF total cell number concentration were largely due to greatly increased numbers of neutrophils, which has also been a consistent finding in several previous studies on urban air particulate exposures in mice and rats (Adamson & Prieditis, 2004;Gavett et al, 2003;GerlofsNijland et al, 2005;Schins et al, 2003). However, in A/J mice, the increase in BALF total cell number has been largely due to increased eosinophil numbers (Walters et al, 2001), suggesting a possibility of significant variations between different mouse Inhalation Toxicology Downloaded from informahealthcare.com by University of Adelaide on 11/17/14…”

Activation of Alveolar Macrophages after Plutonium Oxide Inhalation in Rats: Involvement in the Early Inflammatory Response

“…Endothelial cells may also participate in the actinide-induced inflammatory process (38). Such production of inflammatory mediators by pulmonary cells, including macrophages, also appears to be a frequent feature after inhalation of insoluble particles (39)(40)(41). Macrophages isolated from plutonium-exposed rats have been shown to produce TNF-␣ upon LPS stimulation (4).…”

Health Effects of Fine Particulate Air Pollution: Lines that Connect

“…Fairly consistent associations between PM 2.5 and various cardiopulmonary health end points have been observed, yet the roles of coarse particles and ultrafine particles are yet to be fully resolved, 474 -477 as are the roles of atmospheric secondary inorganic PM. 102 Other characteristics of PM pollution that likely relate to relative toxicity include solubility, 478,479 metal content, 343,480 -485 and surface area and reactivity. 106,486 These characteristics need further study.…”