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Significance of persistent inflammation in respiratory disorders induced by nanoparticles.

Morimoto Y, Izumi H, Kuroda E - J Immunol Res (2014)

Bottom Line: Chemical and physical damage are associated with point mutation by free radicals and double strand brake, respectively.Nanoparticles and asbestos also induce the production of free radicals.In allergic responses, nanoparticles act as Th2 adjuvants to activate Th2 immune responses such as activation of eosinophil and induction of IgE.

View Article: PubMed Central - PubMed

Affiliation: Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan.

ABSTRACT
Pulmonary inflammation, especially persistent inflammation, has been found to play a key role in respiratory disorders induced by nanoparticles in animal models. In inhalation studies and instillation studies of nanomaterials, persistent inflammation is composed of neutrophils and alveolar macrophages, and its pathogenesis is related to chemokines such as the cytokine-induced neutrophil chemoattractant (CINC) family and macrophage inflammatory protein-1α and oxidant stress-related genes such as heme oxygenase-1 (HO-1). DNA damages occur chemically or physically by nanomaterials. Chemical and physical damage are associated with point mutation by free radicals and double strand brake, respectively. The failure of DNA repair and accumulation of mutations might occur when inflammation is prolonged, and finally normal cells could become malignant. These free radicals can not only damage cells but also induce signaling molecules containing immunoreaction. Nanoparticles and asbestos also induce the production of free radicals. In allergic responses, nanoparticles act as Th2 adjuvants to activate Th2 immune responses such as activation of eosinophil and induction of IgE. Taken together, the presence of persistent inflammation may contribute to the pathogenesis of a variety of diseases induced by nanomaterials.

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Related in: MedlinePlus

Hematoxylin and eosin staining of lung sections exposed to 3 mg TiO2 nanoparticles at 3 days after instillation.
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Related In: Results  -  Collection


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fig1: Hematoxylin and eosin staining of lung sections exposed to 3 mg TiO2 nanoparticles at 3 days after instillation.

Mentions: In cases of intratracheal instillation of particles, an excess dose induces the artificial effect of the bolus. We conducted an intratracheal instillation of 3 mg/rat of titanium dioxide nanoparticles [14]. Figure 1 shows a large granulomatous lesion including local accumulation of TiO2 nanoparticles in the bronchoalveolar area 3 days after exposure. These lesions in the lung are not seen in usual inhalation studies. From this point of view, exposure of animals to excess doses of nanoparticles should be avoided. Although the most suitable dose of nanoparticles for the evaluation of harmful effects is not known, 0.2 mg/rat (0.67 mg/kg) of nickel oxide nanoparticles with high toxicity induced persistent neutrophil inflammation in rats [6, 15], and 1 mg (3.3–5 mg/kg) of fullerene and titanium dioxide nanoparticles with low toxicity induced transient inflammation [9, 14, 16]. If the relative harmful effect between nanoparticles is measured under the same weight base, pulmonary responses at doses from 0.2 mg/rat to 1 mg/rat (0.67–5 mg/kg) may be useful, at least partially.


Significance of persistent inflammation in respiratory disorders induced by nanoparticles.

Morimoto Y, Izumi H, Kuroda E - J Immunol Res (2014)

Hematoxylin and eosin staining of lung sections exposed to 3 mg TiO2 nanoparticles at 3 days after instillation.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4109676&req=5

fig1: Hematoxylin and eosin staining of lung sections exposed to 3 mg TiO2 nanoparticles at 3 days after instillation.
Mentions: In cases of intratracheal instillation of particles, an excess dose induces the artificial effect of the bolus. We conducted an intratracheal instillation of 3 mg/rat of titanium dioxide nanoparticles [14]. Figure 1 shows a large granulomatous lesion including local accumulation of TiO2 nanoparticles in the bronchoalveolar area 3 days after exposure. These lesions in the lung are not seen in usual inhalation studies. From this point of view, exposure of animals to excess doses of nanoparticles should be avoided. Although the most suitable dose of nanoparticles for the evaluation of harmful effects is not known, 0.2 mg/rat (0.67 mg/kg) of nickel oxide nanoparticles with high toxicity induced persistent neutrophil inflammation in rats [6, 15], and 1 mg (3.3–5 mg/kg) of fullerene and titanium dioxide nanoparticles with low toxicity induced transient inflammation [9, 14, 16]. If the relative harmful effect between nanoparticles is measured under the same weight base, pulmonary responses at doses from 0.2 mg/rat to 1 mg/rat (0.67–5 mg/kg) may be useful, at least partially.

Bottom Line: Chemical and physical damage are associated with point mutation by free radicals and double strand brake, respectively.Nanoparticles and asbestos also induce the production of free radicals.In allergic responses, nanoparticles act as Th2 adjuvants to activate Th2 immune responses such as activation of eosinophil and induction of IgE.

View Article: PubMed Central - PubMed

Affiliation: Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan.

ABSTRACT
Pulmonary inflammation, especially persistent inflammation, has been found to play a key role in respiratory disorders induced by nanoparticles in animal models. In inhalation studies and instillation studies of nanomaterials, persistent inflammation is composed of neutrophils and alveolar macrophages, and its pathogenesis is related to chemokines such as the cytokine-induced neutrophil chemoattractant (CINC) family and macrophage inflammatory protein-1α and oxidant stress-related genes such as heme oxygenase-1 (HO-1). DNA damages occur chemically or physically by nanomaterials. Chemical and physical damage are associated with point mutation by free radicals and double strand brake, respectively. The failure of DNA repair and accumulation of mutations might occur when inflammation is prolonged, and finally normal cells could become malignant. These free radicals can not only damage cells but also induce signaling molecules containing immunoreaction. Nanoparticles and asbestos also induce the production of free radicals. In allergic responses, nanoparticles act as Th2 adjuvants to activate Th2 immune responses such as activation of eosinophil and induction of IgE. Taken together, the presence of persistent inflammation may contribute to the pathogenesis of a variety of diseases induced by nanomaterials.

Show MeSH
Related in: MedlinePlus