Carbon Nanotubes and Chronic Granulomatous Disease

Barna, Barbara P.; Judson, Marc A.; Thomassen, Mary Jane

doi:10.3390/nano4020508

Cited by 19 publications

(8 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3). Other studies have documented granuloma formation after MWCNT exposure [4–6, 20, 29, 32–34]. Granulomas centrally consist of epithelioid and multinucleated giant macrophages surrounded by activated lymphocytes, typically activated CD4+ T cells [35].…”

Section: Discussionmentioning

confidence: 99%

STAT1-dependent and -independent pulmonary allergic and fibrogenic responses in mice after exposure to tangled versus rod-like multi-walled carbon nanotubes

et al. 2017

View full text Add to dashboard Cite

BackgroundPulmonary toxicity of multi-walled carbon nanotubes (MWCNTs) is influenced by physicochemical characteristics and genetic susceptibility. We hypothesized that contrasting rigidities of tangled (t) versus rod-like (r) MWCNTs would result in differing immunologic or fibrogenic responses in mice and that these responses would be exaggerated in transgenic mice lacking the signal transducer and activator of transcription-1 (STAT1), a susceptible mouse model of pulmonary fibrosis.MethodsMale wild type (Stat1 +/+) and STAT1-deficient (Stat1 −/−) mice were exposed to 4 mg/kg tMWCNTs, rMWCNTs, or vehicle alone via oropharyngeal aspiration and evaluated for inflammation at one and 21 days post-exposure via histopathology, differential cell counts, and cytokine levels in bronchoalveolar lavage fluid (BALF). Granuloma formation, mucous cell metaplasia, and airway fibrosis were evaluated by quantitative morphometry. Airway epithelial cell proliferation was assessed by bromodeoxyuridine (BrdU) incorporation. Cytokine protein levels in BALF and serum IgE levels were measured by ELISA. Lung protein Smad2/3 levels and activation were measured by Western blot. Lung mRNAs were measured by PCR.ResultsThere was a 7-fold difference in rigidity between tMWCNTs and rMWCNTs as determined by static bending ratio. Both MWCNT types resulted in acute inflammation (neutrophils in BALF) after one-day post-exposure, yet only rMWCNTs resulted in chronic inflammation at 21 days as indicated by neutrophil influx and larger granulomas. Both MWCNTs induced BrdU uptake in airway epithelial cells, with the greatest proliferative response observed in rMWCNT-exposed mice after one-day. Only rMWCNTs induced mucous cell metaplasia, but this index was not different between genotypes. Stat1 −/− mice had higher levels of baseline serum IgE than Stat1 +/+ mice. Greater airway fibrosis was observed with rMWCNTs compared to tMWCNTs, and exaggerated airway fibrosis was seen in the Stat1 −/− mouse lungs with rMWCNTs but not tMWCNTs. Increased fibrosis correlated with elevated levels of TGF-β1 protein levels in the BALF of Stat1 −/− mice exposed to rMWCNTs and increased lung Smad2/3 phosphorylation.ConclusionsRigidity plays a key role in the toxicity of MWCNTs and results in increased inflammatory, immunologic, and fibrogenic effects in the lung. STAT1 is an important protective factor in the fibroproliferative response to rMWCNTs, regulating both induced TGF-β1 production and Smad2/3 phosphorylation status. Therefore, both rigidity and genetic susceptibility should be major considerations for risk assessment of MWCNTs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-017-0207-3) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

STAT1-dependent and -independent pulmonary allergic and fibrogenic responses in mice after exposure to tangled versus rod-like multi-walled carbon nanotubes

et al. 2017

View full text Add to dashboard Cite

show abstract

“…For example, nanomaterials like CNTs could interact with immune cells such as platelets, neutrophils, and macrophages. This may lead to the generation of numerous cytokines like interleukins and tumor necrosis factor‐α that are capable of further initiating a series of immune reactions and eventually fibrosis and bronchial granulomas . Alternatively, NPs including SiO 2 , TiO 2 , and hydroxyapatite were capable of increasing cell contractility via massive disruption of the intracellular microtubule assembly without any apparent cytotoxicity, finally resulting in the promotion of strong substrate adhesions and limit of cell motility .…”

Section: Recent Discoveries In Nanotoxicology and Nanomedical Implicamentioning

confidence: 99%

A Safe‐by‐Design Strategy towards Safer Nanomaterials in Nanomedicines

et al. 2019

View full text Add to dashboard Cite

The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adma.201805391.The marriage of nanotechnology and medicine offers new opportunities to fight against human diseases. Benefiting from their unique optical, thermal, magnetic, or redox properties, a wide range of nanomaterials have shown potential in applications such as diagnosis, drug delivery, or tissue repair and regeneration. Despite the considerable success achieved over the past decades, the newly emerging nanomedicines still suffer from an incomplete understanding of their safety risks, and of the relationships between their physicochemical characteristics and safety profiles. Herein, the most important categories of nanomaterials with clinical potential and their toxicological mechanisms are summarized, and then, based on this available information, an overview of the principles in developing safe-by-design nanomaterials for medical applications and of the recent progress in this field is provided. These principles may serve as a starting point to guide the development of more effective safe-by-design strategies and to help identify the major knowledge and skill gaps.

show abstract

“…The biocompatibility is the first and foremost consideration for most applications. Carbon nanotube research has demonstrated that free nano‐dimensional carbon‐based particles can interfere with the metabolism and membrane integrity of cells, leading to potential toxic effects . In addition, if there is degradation of the material, or any mechanism by which nanomaterials can enter the blood stream, the effects of the particles on tissues, such as lungs, liver, and kidneys, and the ability of the body to excrete the materials needs to be considered.…”

Section: Graphene For Tissue Engineeringmentioning

confidence: 99%

Graphite Oxide to Graphene. Biomaterials to Bionics

2015

View full text Add to dashboard Cite

The advent of implantable biomaterials has revolutionized medical treatment, allowing the development of the fields of tissue engineering and medical bionic devices (e.g., cochlea implants to restore hearing, vagus nerve stimulators to control Parkinson's disease, and cardiac pace makers). Similarly, future materials developments are likely to continue to drive development in treatment of disease and disability, or even enhancing human potential. The material requirements for implantable devices are stringent. In all cases they must be nontoxic and provide appropriate mechanical integrity for the application at hand. In the case of scaffolds for tissue regeneration, biodegradability in an appropriate time frame may be required, and for medical bionics electronic conductivity is essential. The emergence of graphene and graphene-family composites has resulted in materials and structures highly relevant to the expansion of the biomaterials inventory available for implantable medical devices. The rich chemistries available are able to ensure properties uncovered in the nanodomain are conveyed into the world of macroscopic devices. Here, the inherent properties of graphene, along with how graphene or structures containing it interface with living cells and the effect of electrical stimulation on nerves and cells, are reviewed.

show abstract

Carbon Nanotubes and Chronic Granulomatous Disease

Cited by 19 publications

References 83 publications

STAT1-dependent and -independent pulmonary allergic and fibrogenic responses in mice after exposure to tangled versus rod-like multi-walled carbon nanotubes

STAT1-dependent and -independent pulmonary allergic and fibrogenic responses in mice after exposure to tangled versus rod-like multi-walled carbon nanotubes

A Safe‐by‐Design Strategy towards Safer Nanomaterials in Nanomedicines

Graphite Oxide to Graphene. Biomaterials to Bionics

Contact Info

Product

Resources

About