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Inhalation of rod-like carbon nanotubes causes unconventional allergic airway inflammation.

Rydman EM, Ilves M, Koivisto AJ, Kinaret PA, Fortino V, Savinko TS, Lehto MT, Pulkkinen V, Vippola M, Hämeri KJ, Matikainen S, Wolff H, Savolainen KM, Greco D, Alenius H - Part Fibre Toxicol (2014)

Bottom Line: However, little is known about the possible effects of CNT on pulmonary allergic diseases, such as asthma.Mast cells were found to partially regulate the inflammation caused by rod-like CNT, but also alveaolar macrophages play an important role in the early stages.These observations emphasize the diverse abilities of CNT to impact the immune system, and they should be taken into account for hazard assessment.

View Article: PubMed Central - PubMed

Affiliation: Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki, Finland. elina.rydman@ttl.fi.

ABSTRACT

Background: Carbon nanotubes (CNT) represent a great promise for technological and industrial development but serious concerns on their health effects have also emerged. Rod-shaped CNT are, in fact, able to induce asbestos-like pathogenicity in mice including granuloma formation in abdominal cavity and sub-pleural fibrosis. Exposure to CNT, especially in the occupational context, happens mainly by inhalation. However, little is known about the possible effects of CNT on pulmonary allergic diseases, such as asthma.

Methods: We exposed mice by inhalation to two types of multi-walled CNT, rigid rod-like and flexible tangled CNT, for four hours a day once or on four consecutive days. Early events were monitored immediately and 24 hours after the single inhalation exposure and the four day exposure mimicked an occupational work week. Mast cell deficient mice were used to evaluate the role of mast cells in the occurring inflammation.

Results: Here we show that even a short-term inhalation of the rod-like CNT induces novel innate immunity-mediated allergic-like airway inflammation in healthy mice. Marked eosinophilia was accompanied by mucus hypersecretion, AHR and the expression of Th2-type cytokines. Exploration of the early events by transcriptomics analysis reveals that a single 4-h exposure to rod-shaped CNT, but not to tangled CNT, causes a radical up-regulation of genes involved in innate immunity and cytokine/chemokine pathways. Mast cells were found to partially regulate the inflammation caused by rod-like CNT, but also alveaolar macrophages play an important role in the early stages.

Conclusions: These observations emphasize the diverse abilities of CNT to impact the immune system, and they should be taken into account for hazard assessment.

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Related in: MedlinePlus

Mast cells play a partial role in the development of rCNT-triggered asthma. Wild type (WT) C57BL/6 mice and mast cell deficient KitW-sh mice in C57BL/6 background were exposed to rCNT for 4 h/day on 4 consecutive days and were sacrificed on day 5. a: BAL cell counts showed that mast cells affect the migration of eosinophils but not neutrophils into the lungs. b: the numbers of PAS+ cells did not differ in WT and KitW-sh mice indicating that mast cells do not regulate the activation of goblet cells. c: the mRNA expression levels measured in lung tissue revealed a significant down-regulation of Th2 type cytokine Il-13 in KitW-sh mice compared with WT mice. PAS+ cell counts (b) represent the average of positive cells per 200 μm of bronchus surface counted from three bronchi per mouse in control group and six bronchi per mouse in CNT-exposed groups (n = 7-9). mRNA expression levels in c are presented as fold changes relative to untreated control mice of the corresponding strain (n = 7-9). *P < 0.05; **P < 0.01; ***P < 0.001.
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Fig3: Mast cells play a partial role in the development of rCNT-triggered asthma. Wild type (WT) C57BL/6 mice and mast cell deficient KitW-sh mice in C57BL/6 background were exposed to rCNT for 4 h/day on 4 consecutive days and were sacrificed on day 5. a: BAL cell counts showed that mast cells affect the migration of eosinophils but not neutrophils into the lungs. b: the numbers of PAS+ cells did not differ in WT and KitW-sh mice indicating that mast cells do not regulate the activation of goblet cells. c: the mRNA expression levels measured in lung tissue revealed a significant down-regulation of Th2 type cytokine Il-13 in KitW-sh mice compared with WT mice. PAS+ cell counts (b) represent the average of positive cells per 200 μm of bronchus surface counted from three bronchi per mouse in control group and six bronchi per mouse in CNT-exposed groups (n = 7-9). mRNA expression levels in c are presented as fold changes relative to untreated control mice of the corresponding strain (n = 7-9). *P < 0.05; **P < 0.01; ***P < 0.001.

Mentions: Mast cells are one of the main mediators in immediate allergic reactions. To explore the involvement of this cell type in rCNT-induced inflammation, mast cell deficient KitW-sh mice were used. 24 h after 4-day inhalation exposure to rCNT, significantly elevated number of eosinophils was found in KitW-sh as compared to wild type (WT) C57BL/6 mice, however, no significant differences were seen in the number of neutrophils (Figure 3a) and lymphocytes (Additional file 2a). Mast cells were not found to mediate the activation of goblet cells as the number of periodic acid-Schiff (PAS)+ cells were comparable between both strains after rCNT exposure (Figure 3b). While rCNT-induced mRNA expression of Il-13 was highly dependent on mast cells (Figure 3c), production of Ccl11, Ccl24 and Ccl17 was not significantly affected by these cells (Additional file 2b).Figure 3


Inhalation of rod-like carbon nanotubes causes unconventional allergic airway inflammation.

Rydman EM, Ilves M, Koivisto AJ, Kinaret PA, Fortino V, Savinko TS, Lehto MT, Pulkkinen V, Vippola M, Hämeri KJ, Matikainen S, Wolff H, Savolainen KM, Greco D, Alenius H - Part Fibre Toxicol (2014)

Mast cells play a partial role in the development of rCNT-triggered asthma. Wild type (WT) C57BL/6 mice and mast cell deficient KitW-sh mice in C57BL/6 background were exposed to rCNT for 4 h/day on 4 consecutive days and were sacrificed on day 5. a: BAL cell counts showed that mast cells affect the migration of eosinophils but not neutrophils into the lungs. b: the numbers of PAS+ cells did not differ in WT and KitW-sh mice indicating that mast cells do not regulate the activation of goblet cells. c: the mRNA expression levels measured in lung tissue revealed a significant down-regulation of Th2 type cytokine Il-13 in KitW-sh mice compared with WT mice. PAS+ cell counts (b) represent the average of positive cells per 200 μm of bronchus surface counted from three bronchi per mouse in control group and six bronchi per mouse in CNT-exposed groups (n = 7-9). mRNA expression levels in c are presented as fold changes relative to untreated control mice of the corresponding strain (n = 7-9). *P < 0.05; **P < 0.01; ***P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4215016&req=5

Fig3: Mast cells play a partial role in the development of rCNT-triggered asthma. Wild type (WT) C57BL/6 mice and mast cell deficient KitW-sh mice in C57BL/6 background were exposed to rCNT for 4 h/day on 4 consecutive days and were sacrificed on day 5. a: BAL cell counts showed that mast cells affect the migration of eosinophils but not neutrophils into the lungs. b: the numbers of PAS+ cells did not differ in WT and KitW-sh mice indicating that mast cells do not regulate the activation of goblet cells. c: the mRNA expression levels measured in lung tissue revealed a significant down-regulation of Th2 type cytokine Il-13 in KitW-sh mice compared with WT mice. PAS+ cell counts (b) represent the average of positive cells per 200 μm of bronchus surface counted from three bronchi per mouse in control group and six bronchi per mouse in CNT-exposed groups (n = 7-9). mRNA expression levels in c are presented as fold changes relative to untreated control mice of the corresponding strain (n = 7-9). *P < 0.05; **P < 0.01; ***P < 0.001.
Mentions: Mast cells are one of the main mediators in immediate allergic reactions. To explore the involvement of this cell type in rCNT-induced inflammation, mast cell deficient KitW-sh mice were used. 24 h after 4-day inhalation exposure to rCNT, significantly elevated number of eosinophils was found in KitW-sh as compared to wild type (WT) C57BL/6 mice, however, no significant differences were seen in the number of neutrophils (Figure 3a) and lymphocytes (Additional file 2a). Mast cells were not found to mediate the activation of goblet cells as the number of periodic acid-Schiff (PAS)+ cells were comparable between both strains after rCNT exposure (Figure 3b). While rCNT-induced mRNA expression of Il-13 was highly dependent on mast cells (Figure 3c), production of Ccl11, Ccl24 and Ccl17 was not significantly affected by these cells (Additional file 2b).Figure 3

Bottom Line: However, little is known about the possible effects of CNT on pulmonary allergic diseases, such as asthma.Mast cells were found to partially regulate the inflammation caused by rod-like CNT, but also alveaolar macrophages play an important role in the early stages.These observations emphasize the diverse abilities of CNT to impact the immune system, and they should be taken into account for hazard assessment.

View Article: PubMed Central - PubMed

Affiliation: Nanosafety Research Centre, Finnish Institute of Occupational Health, Helsinki, Finland. elina.rydman@ttl.fi.

ABSTRACT

Background: Carbon nanotubes (CNT) represent a great promise for technological and industrial development but serious concerns on their health effects have also emerged. Rod-shaped CNT are, in fact, able to induce asbestos-like pathogenicity in mice including granuloma formation in abdominal cavity and sub-pleural fibrosis. Exposure to CNT, especially in the occupational context, happens mainly by inhalation. However, little is known about the possible effects of CNT on pulmonary allergic diseases, such as asthma.

Methods: We exposed mice by inhalation to two types of multi-walled CNT, rigid rod-like and flexible tangled CNT, for four hours a day once or on four consecutive days. Early events were monitored immediately and 24 hours after the single inhalation exposure and the four day exposure mimicked an occupational work week. Mast cell deficient mice were used to evaluate the role of mast cells in the occurring inflammation.

Results: Here we show that even a short-term inhalation of the rod-like CNT induces novel innate immunity-mediated allergic-like airway inflammation in healthy mice. Marked eosinophilia was accompanied by mucus hypersecretion, AHR and the expression of Th2-type cytokines. Exploration of the early events by transcriptomics analysis reveals that a single 4-h exposure to rod-shaped CNT, but not to tangled CNT, causes a radical up-regulation of genes involved in innate immunity and cytokine/chemokine pathways. Mast cells were found to partially regulate the inflammation caused by rod-like CNT, but also alveaolar macrophages play an important role in the early stages.

Conclusions: These observations emphasize the diverse abilities of CNT to impact the immune system, and they should be taken into account for hazard assessment.

Show MeSH
Related in: MedlinePlus