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Impaired clearance and enhanced pulmonary inflammatory/fibrotic response to carbon nanotubes in myeloperoxidase-deficient mice.

Shvedova AA, Kapralov AA, Feng WH, Kisin ER, Murray AR, Mercer RR, St Croix CM, Lang MA, Watkins SC, Konduru NV, Allen BL, Conroy J, Kotchey GP, Mohamed BM, Meade AD, Volkov Y, Star A, Fadeel B, Kagan VE - PLoS ONE (2012)

Bottom Line: Advancement of biomedical applications of carbonaceous nanomaterials is hampered by their biopersistence and pro-inflammatory action in vivo.Here, we used myeloperoxidase knockout B6.129X1-MPO (MPO k/o) mice and showed that oxidation and clearance of single walled carbon nanotubes (SWCNT) from the lungs of these animals after pharyngeal aspiration was markedly less effective whereas the inflammatory response was more robust than in wild-type C57Bl/6 mice.Our results provide direct evidence for the participation of MPO - one of the key-orchestrators of inflammatory response - in the in vivo pulmonary oxidative biodegradation of SWCNT and suggest new ways to control the biopersistence of nanomaterials through genetic or pharmacological manipulations.

View Article: PubMed Central - PubMed

Affiliation: Pathology and Physiology Research Branch, Health Effects Lab Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, United States of America.

ABSTRACT
Advancement of biomedical applications of carbonaceous nanomaterials is hampered by their biopersistence and pro-inflammatory action in vivo. Here, we used myeloperoxidase knockout B6.129X1-MPO (MPO k/o) mice and showed that oxidation and clearance of single walled carbon nanotubes (SWCNT) from the lungs of these animals after pharyngeal aspiration was markedly less effective whereas the inflammatory response was more robust than in wild-type C57Bl/6 mice. Our results provide direct evidence for the participation of MPO - one of the key-orchestrators of inflammatory response - in the in vivo pulmonary oxidative biodegradation of SWCNT and suggest new ways to control the biopersistence of nanomaterials through genetic or pharmacological manipulations.

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Characterization of pulmonary inflammatory responses to SWCNT in w/t and MPO k/o mice at day 1 after pharyngeal aspiration exposure.a–c. Levels of pro-inflammatory cytokines (a - TNF-α; b - IL-6; c – MCP-1) in BAL fluid of w/t and MPO k/o mice. Mean ± SEM (n = 6 mice/group). *p<0.05, vs control PBS-exposed mice. d. Content of PMNs in BAL fluid of w/t and MPO k/o mice. Mean ± SEM (n = 6 mice/group). *p<0.05, vs control PBS-exposed mice. e. Typical microscopic images of inflammatory cells in BAL fluid with SWCNT inclusions (red arrows). f. Content of PMNs with engulfed SWCNT in BAL fluid of w/t and MPO k/o mice. Mean ± SEM (n = 6 mice/group). *p<0.05, vs w/t mice.
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pone-0030923-g001: Characterization of pulmonary inflammatory responses to SWCNT in w/t and MPO k/o mice at day 1 after pharyngeal aspiration exposure.a–c. Levels of pro-inflammatory cytokines (a - TNF-α; b - IL-6; c – MCP-1) in BAL fluid of w/t and MPO k/o mice. Mean ± SEM (n = 6 mice/group). *p<0.05, vs control PBS-exposed mice. d. Content of PMNs in BAL fluid of w/t and MPO k/o mice. Mean ± SEM (n = 6 mice/group). *p<0.05, vs control PBS-exposed mice. e. Typical microscopic images of inflammatory cells in BAL fluid with SWCNT inclusions (red arrows). f. Content of PMNs with engulfed SWCNT in BAL fluid of w/t and MPO k/o mice. Mean ± SEM (n = 6 mice/group). *p<0.05, vs w/t mice.

Mentions: Upon pharyngeal aspiration, SWCNT elicited typical inflammatory responses in w/t and MPO k/o mice documented by increased production of pro-inflammatory cytokines (TNF-α, IL-6 and MCP-1) 1 day after the exposure (Fig. 1a, b, c). BAL cytology indicated a robust and early (day 1) accumulation of neutrophils - slightly weaker in MPO k/o mice vs w/t animals (Fig. 1d), followed by a sequential appearance of macrophages in both groups of animals (with a peak at day 7) (data not shown) [4]. At day 28 post exposure, the amounts of PMN in BAL fluid from exposed MPO k/o mice and w/t mice are not different from those in the respective control groups of animals (Fig. 1d). In BAL, phagocytized SWCNT were detected inside PMNs and macrophages (Fig. 1e). Because of the enrichment of PMNs with MPO, we compared the SWCNT content in these cells. An ∼10 times greater number of PMNs from MPO k/o mice had SWCNT inclusions than those from w/t animals (Fig. 1f), in agreement with the lack of MPO-driven biodegradation in MPO k/o mice.


Impaired clearance and enhanced pulmonary inflammatory/fibrotic response to carbon nanotubes in myeloperoxidase-deficient mice.

Shvedova AA, Kapralov AA, Feng WH, Kisin ER, Murray AR, Mercer RR, St Croix CM, Lang MA, Watkins SC, Konduru NV, Allen BL, Conroy J, Kotchey GP, Mohamed BM, Meade AD, Volkov Y, Star A, Fadeel B, Kagan VE - PLoS ONE (2012)

Characterization of pulmonary inflammatory responses to SWCNT in w/t and MPO k/o mice at day 1 after pharyngeal aspiration exposure.a–c. Levels of pro-inflammatory cytokines (a - TNF-α; b - IL-6; c – MCP-1) in BAL fluid of w/t and MPO k/o mice. Mean ± SEM (n = 6 mice/group). *p<0.05, vs control PBS-exposed mice. d. Content of PMNs in BAL fluid of w/t and MPO k/o mice. Mean ± SEM (n = 6 mice/group). *p<0.05, vs control PBS-exposed mice. e. Typical microscopic images of inflammatory cells in BAL fluid with SWCNT inclusions (red arrows). f. Content of PMNs with engulfed SWCNT in BAL fluid of w/t and MPO k/o mice. Mean ± SEM (n = 6 mice/group). *p<0.05, vs w/t mice.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3316527&req=5

pone-0030923-g001: Characterization of pulmonary inflammatory responses to SWCNT in w/t and MPO k/o mice at day 1 after pharyngeal aspiration exposure.a–c. Levels of pro-inflammatory cytokines (a - TNF-α; b - IL-6; c – MCP-1) in BAL fluid of w/t and MPO k/o mice. Mean ± SEM (n = 6 mice/group). *p<0.05, vs control PBS-exposed mice. d. Content of PMNs in BAL fluid of w/t and MPO k/o mice. Mean ± SEM (n = 6 mice/group). *p<0.05, vs control PBS-exposed mice. e. Typical microscopic images of inflammatory cells in BAL fluid with SWCNT inclusions (red arrows). f. Content of PMNs with engulfed SWCNT in BAL fluid of w/t and MPO k/o mice. Mean ± SEM (n = 6 mice/group). *p<0.05, vs w/t mice.
Mentions: Upon pharyngeal aspiration, SWCNT elicited typical inflammatory responses in w/t and MPO k/o mice documented by increased production of pro-inflammatory cytokines (TNF-α, IL-6 and MCP-1) 1 day after the exposure (Fig. 1a, b, c). BAL cytology indicated a robust and early (day 1) accumulation of neutrophils - slightly weaker in MPO k/o mice vs w/t animals (Fig. 1d), followed by a sequential appearance of macrophages in both groups of animals (with a peak at day 7) (data not shown) [4]. At day 28 post exposure, the amounts of PMN in BAL fluid from exposed MPO k/o mice and w/t mice are not different from those in the respective control groups of animals (Fig. 1d). In BAL, phagocytized SWCNT were detected inside PMNs and macrophages (Fig. 1e). Because of the enrichment of PMNs with MPO, we compared the SWCNT content in these cells. An ∼10 times greater number of PMNs from MPO k/o mice had SWCNT inclusions than those from w/t animals (Fig. 1f), in agreement with the lack of MPO-driven biodegradation in MPO k/o mice.

Bottom Line: Advancement of biomedical applications of carbonaceous nanomaterials is hampered by their biopersistence and pro-inflammatory action in vivo.Here, we used myeloperoxidase knockout B6.129X1-MPO (MPO k/o) mice and showed that oxidation and clearance of single walled carbon nanotubes (SWCNT) from the lungs of these animals after pharyngeal aspiration was markedly less effective whereas the inflammatory response was more robust than in wild-type C57Bl/6 mice.Our results provide direct evidence for the participation of MPO - one of the key-orchestrators of inflammatory response - in the in vivo pulmonary oxidative biodegradation of SWCNT and suggest new ways to control the biopersistence of nanomaterials through genetic or pharmacological manipulations.

View Article: PubMed Central - PubMed

Affiliation: Pathology and Physiology Research Branch, Health Effects Lab Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, United States of America.

ABSTRACT
Advancement of biomedical applications of carbonaceous nanomaterials is hampered by their biopersistence and pro-inflammatory action in vivo. Here, we used myeloperoxidase knockout B6.129X1-MPO (MPO k/o) mice and showed that oxidation and clearance of single walled carbon nanotubes (SWCNT) from the lungs of these animals after pharyngeal aspiration was markedly less effective whereas the inflammatory response was more robust than in wild-type C57Bl/6 mice. Our results provide direct evidence for the participation of MPO - one of the key-orchestrators of inflammatory response - in the in vivo pulmonary oxidative biodegradation of SWCNT and suggest new ways to control the biopersistence of nanomaterials through genetic or pharmacological manipulations.

Show MeSH
Related in: MedlinePlus