Agglomerates of ultrafine particles of elemental carbon and TiO2 induce generation of lipid mediators in alveolar macrophages.

Abstract

Agglomerates of ultrafine particles (AUFPs) may cause adverse health effects because of their large surface area. To evaluate physiologic responses of immune cells, we studied whether agglomerates of 77-nm elemental carbon [(EC); specific surface area 750 m2/g] and 21 nm titanium dioxide (TiO(2) particles (specific surface area 50 m(2)/g) affect the release of lipid mediators by alveolar macrophages (AMs). After 60-min incubation with 1 microg/mL AUFP-EC (corresponding to 7.5 cm(2) particle surface area), canine AMs (1 x 10(6) cells/mL) released arachidonic acid (AA) and the cyclooxygenase (COX) products prostaglandin E(2) (PGE(2), thromboxane B(2), and 12-hydroxyheptadecatrienoic acid but not 5-lipoxygenase (5-LO) products. AUFP-TiO(2) with a 10-fold higher mass (10 microg/mL) than AUFP-EC, but a similar particle surface area (5 cm(2) also induced AMs to release AA and COX products. Agglomerates of 250 nm TiO(2) particles (specific surface area 6.5 m(2)/g) at 100 microg/mL mass concentration (particle surface area 6.5 cm(2) showed the same response. Interestingly, 75 cm(2)/mL surface area of AUFP-EC and 16 cm(2)/mL surface area of AUFP-TiO(2) additionally induced the release of the 5-LO products leukotriene B(4) and 5-hydroxyeicosatetraenoic acid. Respiratory burst activity of stimulated canine neutrophils was partially suppressed by supernatants of AMs treated with various mass concentrations of the three types of particles. Inhibition of neutrophil activity was abolished by supernatants of AMs treated with COX inhibitors prior to AUFP-incubation. This indicates that anti-inflammatory properties of PGE(2) dominate the overall response of lipid mediators released by AUFP-affected AMs. In conclusion, our data indicate that surface area rather than mass concentration determines the effect of AUFPs, and that activation of phospholipase A(subscript)2(/subscript) and COX pathway occurs at a lower particle surface area than that of 5-LO-pathway. We hypothesize a protective role of PGE(2) in downregulating potential inflammatory reactions induced by ultrafine particles.

Lipoxygenase Pathway Mediates Increases of Airway Resistance and Lung Inflation Induced by Exposure to Nanotitanium Dioxide in Rats

“…The phagocytotic ability of macrophages is impaired following high-dose nTiO 2 inhalation [25], and its sensitivity to the chemotactic agent complement 5a is enhanced [14], facilitating further accumulation of inflammatory cells. nTiO 2 are known to generate lipid mediators in alveolar macrophages [26]. The oxidation of lipids can be channeled down either the cyclooxygenase or the lipoxygenase pathway.…”

Induction of Inflammasome-dependent Pyroptosis by Carbon Black Nanoparticles

“…There are several explanations for this increased toxicity, including the increased surface area of nanoparticles (10,12,14,(17)(18)(19)(20)(21)(22). In a previous study, acute adverse effects of different types of carbonaceous nanoparticles instilled in mice strongly correlated with particle size and surface area (23).…”

“…Although bulk elemental carbon is considered chemically inert (as in diamond and graphite), seemingly inert substances have been shown to elicit an inflammatory response when exposure occurs with nanoscale particles compared with an equivalent mass dose of larger particles (11-15). Carbon black (CB) 2 nanoparticles can cause cytotoxic injury, increase levels of proinflammatory chemokines, and inhibit cell growth (16).There are several explanations for this increased toxicity, including the increased surface area of nanoparticles (10,12,14,(17)(18)(19)(20)(21)(22). In a previous study, acute adverse effects of different types of carbonaceous nanoparticles instilled in mice strongly correlated with particle size and surface area (23).…”

Ultrafine carbon particles induce interleukin-8 gene transcription and p38 MAPK activation in normal human bronchial epithelial cells

“…A number of epidemiological studies suggest that increased ultrafine particles associated with PM are potent contributors to decreased pulmonary function, increased frequency of symptoms, and medication use in asthmatics (15,42,60). A number of epidemiological, animal, and in vitro studies indicate that exposure to ultrafine particles causes proinflammatory events characterized by oxidative stress, lipid mediator synthesis, transcription factor activation, and cytokine release (2,4,32,55). These particles are reported to be more inflammogenic than both fine and coarse particles (3,31).…”