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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

Alveolar macrophages and mast cells mediate the early inflammatory and pro-allergic responses induced by rCNT. a,b: BAL and lung tissue were collected from C57BL/6 mice exposed to rCNT for 4 h and sacrificed either immediately or on the following day. Comparison of mRNA expression levels of cytokines/chemokines in BAL cells (a) and lung tissue (b) showing that pro-inflammatory cytokines Il-1β and Tnf-α are produced by alveolar macrophages which are the major cell type in BAL at early time points (data not shown) while Th2-promoting cytokine Il-33, and eosinophil-attracting chemokine Ccl17 are expressed in BAL cells as well as in other cells types present in lung tissue. c: levels of Th2 type cytokines Il-13 and Il-4 in lungs were dependent on the presence of mast cells as the expression of these cytokines was significantly lower in KitW-sh mice exposed to rCNT for 4 h and sacrificed on the next day. mRNA expression levels in a and b are presented as fold changes relative to untreated control mice (n = 5-8). In c, values indicate fold changes compared with control mice of the corresponding strain (n = 7-9). *P < 0.05; **P < 0.01; ***P < 0.001. C, untreated control group.
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Fig5: Alveolar macrophages and mast cells mediate the early inflammatory and pro-allergic responses induced by rCNT. a,b: BAL and lung tissue were collected from C57BL/6 mice exposed to rCNT for 4 h and sacrificed either immediately or on the following day. Comparison of mRNA expression levels of cytokines/chemokines in BAL cells (a) and lung tissue (b) showing that pro-inflammatory cytokines Il-1β and Tnf-α are produced by alveolar macrophages which are the major cell type in BAL at early time points (data not shown) while Th2-promoting cytokine Il-33, and eosinophil-attracting chemokine Ccl17 are expressed in BAL cells as well as in other cells types present in lung tissue. c: levels of Th2 type cytokines Il-13 and Il-4 in lungs were dependent on the presence of mast cells as the expression of these cytokines was significantly lower in KitW-sh mice exposed to rCNT for 4 h and sacrificed on the next day. mRNA expression levels in a and b are presented as fold changes relative to untreated control mice (n = 5-8). In c, values indicate fold changes compared with control mice of the corresponding strain (n = 7-9). *P < 0.05; **P < 0.01; ***P < 0.001. C, untreated control group.

Mentions: To investigate the involvement of macrophages in the early stages of rCNT-triggered reactions, we exposed C57BL/6 mice for 4 h and collected BAL and lung tissue samples immediately or 24 h after the exposure. Since macrophages are the major cell type in BAL at early stages of the inflammatory response, we compared the mRNA expression of pro-inflammatory and pro-allergic cytokines in BAL cells and lung tissue (Figure 5a,b). We found that Il-1β and Tnf-α are produced mainly by alveolar macrophages while Th2-promoting cytokine Il-33, and eosinophil-attracting chemokine Ccl17 are expressed in BAL cells as well as in other cell types present in lung tissue. In addition, we found that BAL macrophages express Ccl2 and Ccl7, which may contribute to the stimulation of monocyte recruitment to the site of inflammation (Additional file 7).Figure 5


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)

Alveolar macrophages and mast cells mediate the early inflammatory and pro-allergic responses induced by rCNT. a,b: BAL and lung tissue were collected from C57BL/6 mice exposed to rCNT for 4 h and sacrificed either immediately or on the following day. Comparison of mRNA expression levels of cytokines/chemokines in BAL cells (a) and lung tissue (b) showing that pro-inflammatory cytokines Il-1β and Tnf-α are produced by alveolar macrophages which are the major cell type in BAL at early time points (data not shown) while Th2-promoting cytokine Il-33, and eosinophil-attracting chemokine Ccl17 are expressed in BAL cells as well as in other cells types present in lung tissue. c: levels of Th2 type cytokines Il-13 and Il-4 in lungs were dependent on the presence of mast cells as the expression of these cytokines was significantly lower in KitW-sh mice exposed to rCNT for 4 h and sacrificed on the next day. mRNA expression levels in a and b are presented as fold changes relative to untreated control mice (n = 5-8). In c, values indicate fold changes compared with control mice of the corresponding strain (n = 7-9). *P < 0.05; **P < 0.01; ***P < 0.001. C, untreated control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Fig5: Alveolar macrophages and mast cells mediate the early inflammatory and pro-allergic responses induced by rCNT. a,b: BAL and lung tissue were collected from C57BL/6 mice exposed to rCNT for 4 h and sacrificed either immediately or on the following day. Comparison of mRNA expression levels of cytokines/chemokines in BAL cells (a) and lung tissue (b) showing that pro-inflammatory cytokines Il-1β and Tnf-α are produced by alveolar macrophages which are the major cell type in BAL at early time points (data not shown) while Th2-promoting cytokine Il-33, and eosinophil-attracting chemokine Ccl17 are expressed in BAL cells as well as in other cells types present in lung tissue. c: levels of Th2 type cytokines Il-13 and Il-4 in lungs were dependent on the presence of mast cells as the expression of these cytokines was significantly lower in KitW-sh mice exposed to rCNT for 4 h and sacrificed on the next day. mRNA expression levels in a and b are presented as fold changes relative to untreated control mice (n = 5-8). In c, values indicate fold changes compared with control mice of the corresponding strain (n = 7-9). *P < 0.05; **P < 0.01; ***P < 0.001. C, untreated control group.
Mentions: To investigate the involvement of macrophages in the early stages of rCNT-triggered reactions, we exposed C57BL/6 mice for 4 h and collected BAL and lung tissue samples immediately or 24 h after the exposure. Since macrophages are the major cell type in BAL at early stages of the inflammatory response, we compared the mRNA expression of pro-inflammatory and pro-allergic cytokines in BAL cells and lung tissue (Figure 5a,b). We found that Il-1β and Tnf-α are produced mainly by alveolar macrophages while Th2-promoting cytokine Il-33, and eosinophil-attracting chemokine Ccl17 are expressed in BAL cells as well as in other cell types present in lung tissue. In addition, we found that BAL macrophages express Ccl2 and Ccl7, which may contribute to the stimulation of monocyte recruitment to the site of inflammation (Additional file 7).Figure 5

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