Tim4 Recognizes Carbon Nanotubes and Mediates Frustrated Phagocytosis Leading to Granuloma Formation

2020 ◽  
Author(s):  
Satoshi Omori ◽  
Misato Tsugita ◽  
Yasuto Hoshikawa ◽  
Masanobu Morita ◽  
Shin-Ichiro Yamaguchi ◽  
...  
Author(s):  
James C. Bonner

The rapidly evolving field of nanotechnology offers many potential societal and economic benefits. Carbon Nanotubes (CNTs) are one of the most widely produced engineered nanomaterials and have diverse applications in engineering, electronics, and medicine. They have also been extensively investigated for their toxicological properties. Studies with rodents indicate that CNTs can cause lung fibrosis or granuloma formation, exacerbate pre-existing respiratory disease, cause injury to the sensitive pleural lining of the lungs, and have systemic immunosuppressive effects. CNTs have also been reported to cause genotoxic effects on cultured cells. The fiber-like structure of CNTs has led to comparisons with asbestos fibers; yet the debate over whether CNTs cause mesothelioma remains highly controversial, and evidence thus far is lacking. The aim of this chapter is to overview the evidence in rodent models that CNTs cause lung disease and to discuss the potential of CNTs to cause adverse immune, fibrogenic, or carcinogenic effects in humans as a result of occupational, consumer, or environmental exposure.


Cell Reports ◽  
2021 ◽  
Vol 34 (6) ◽  
pp. 108734 ◽  
Author(s):  
Satoshi Omori ◽  
Misato Tsugita ◽  
Yasuto Hoshikawa ◽  
Masanobu Morita ◽  
Fumiya Ito ◽  
...  

Carbon ◽  
2007 ◽  
Vol 45 (9) ◽  
pp. 1743-1756 ◽  
Author(s):  
D.M. Brown ◽  
I.A. Kinloch ◽  
U. Bangert ◽  
A.H. Windle ◽  
D.M. Walter ◽  
...  

2017 ◽  
pp. 1476-1491
Author(s):  
James C. Bonner

The rapidly evolving field of nanotechnology offers many potential societal and economic benefits. Carbon Nanotubes (CNTs) are one of the most widely produced engineered nanomaterials and have diverse applications in engineering, electronics, and medicine. They have also been extensively investigated for their toxicological properties. Studies with rodents indicate that CNTs can cause lung fibrosis or granuloma formation, exacerbate pre-existing respiratory disease, cause injury to the sensitive pleural lining of the lungs, and have systemic immunosuppressive effects. CNTs have also been reported to cause genotoxic effects on cultured cells. The fiber-like structure of CNTs has led to comparisons with asbestos fibers; yet the debate over whether CNTs cause mesothelioma remains highly controversial, and evidence thus far is lacking. The aim of this chapter is to overview the evidence in rodent models that CNTs cause lung disease and to discuss the potential of CNTs to cause adverse immune, fibrogenic, or carcinogenic effects in humans as a result of occupational, consumer, or environmental exposure.


2021 ◽  
Vol 23 (1) ◽  
pp. 47
Author(s):  
Eman Soliman ◽  
Sophia Bhalla ◽  
Ahmed E. M. Elhassanny ◽  
Anagha Malur ◽  
David Ogburn ◽  
...  

The use of carbon nanotubes has increased in the past few decades. Carbon nanotubes are implicated in the pathogenesis of pulmonary sarcoidosis, a chronic granulomatous inflammatory condition. We developed a murine model of chronic granulomatous inflammation using multiwall carbon nanotubes (MWCNT) to investigate mechanisms of granuloma formation. Using this model, we demonstrated that myeloid deficiency of ATP-binding cassette (ABC) cholesterol transporter (ABCG1) promotes granuloma formation and fibrosis with MWCNT instillation; however, the mechanism remains unclear. Our previous studies showed that MWCNT induced apoptosis in bronchoalveolar lavage (BAL) cells of wild-type (C57BL/6) mice. Given that continual apoptosis causes persistent severe lung inflammation, we hypothesized that ABCG1 deficiency would increase MWCNT-induced apoptosis thereby promoting granulomatous inflammation and fibrosis. To test our hypothesis, we utilized myeloid-specific ABCG1 knockout (ABCG1 KO) mice. Our results demonstrate that MWCNT instillation enhances pulmonary fibrosis in ABCG1 KO mice compared to wild-type controls. Enhanced fibrosis is indicated by increased trichrome staining and transforming growth factor-beta (TGF-β) expression in lungs, together with an increased expression of TGF-β related signaling molecules, interleukin-13 (IL-13) and Smad-3. MWCNT induced more apoptosis in BAL cells of ABCG1 KO mice. Initiation of apoptosis is most likely mediated by the extrinsic pathway since caspase 8 activity and Fas expression are significantly higher in MWCNT instilled ABCG1 KO mice compared to the wild type. In addition, TUNEL staining shows that ABCG1 KO mice instilled with MWCNT have a higher percentage of TUNEL positive BAL cells and more efferocytosis than the WT control. Furthermore, BAL cells of ABCG1 KO mice instilled with MWCNT exhibit an increase in efferocytosis markers, milk fat globule-EGF factor 8 (MFG-E8) and integrin β3. Therefore, our observations suggest that ABCG1 deficiency promotes pulmonary fibrosis by MWCNT, and this effect may be due to an increase in apoptosis and efferocytosis in BAL cells.


2021 ◽  
Vol 22 (20) ◽  
pp. 11019
Author(s):  
David Ogburn ◽  
Sophia Bhalla ◽  
Nan Leffler ◽  
Arjun Mohan ◽  
Anagha Malur ◽  
...  

Sarcoidosis is a chronic disease with unknown etiology and pathophysiology, characterized by granuloma formation. Matrix Metalloproteinase-12 (MMP12) is an elastase implicated in active granulomatous sarcoidosis. Previously, we reported that oropharyngeal instillation of multiwall carbon nanotubes (MWCNT) into C57Bl/6 mice induced sarcoid-like granulomas and upregulation of MMP12. When Mmp12 knock-out (KO) mice were instilled with MWCNT, granuloma formation occurred 10 days post-instillation but subsequently resolved at 60 days. Thus, we concluded that MMP12 was essential to granuloma persistence. The aim of the current study was to identify potential mechanisms of granuloma resolution in Mmp12KO mice. Strikingly, an M2 macrophage phenotype was present in Mmp12KO but not in C57Bl/6 mice. Between 10 and 60 days, macrophage populations in MWCNT-instilled Mmp12KO mice demonstrated an M2c to M2a phenotypic shift, with elevations in levels of IL-13, an M2 subtype-regulating factor. Furthermore, the M2 inducer, Apolipoprotein E (ApoE), and Matrix Metalloproteinase-14 (MMP14), a promoter of collagen degradation, were upregulated in 60-day MWCNT-instilled Mmp12KO mice. In conclusion, alveolar macrophages express two M2 phenotypes in Mmp12KO mice: M2c at 10 days when granulomas form, and M2a at 60 days when granulomas are resolving. Findings suggest that granuloma resolution in 60-day Mmp12KO mice requires an M2a macrophage phenotype.


Author(s):  
Jun Jiao

HREM studies of the carbonaceous material deposited on the cathode of a Huffman-Krätschmer arc reactor have shown a rich variety of multiple-walled nano-clusters of different shapes and forms. The preparation of the samples, as well as the variety of cluster shapes, including triangular, rhombohedral and pentagonal projections, are described elsewhere.The close registry imposed on the nanotubes, focuses attention on the cluster growth mechanism. The strict parallelism in the graphitic separation of the tube walls is maintained through changes of form and size, often leading to 180° turns, and accommodating neighboring clusters and defects. Iijima et. al. have proposed a growth scheme in terms of pentagonal and heptagonal defects and their combinations in a hexagonal graphitic matrix, the first bending the surface inward, and the second outward. We report here HREM observations that support Iijima’s suggestions, and add some new features that refine the interpretation of the growth mechanism. The structural elements of our observations are briefly summarized in the following four micrographs, taken in a Hitachi H-8100 TEM operating at an accelerating voltage of 200 kV and with a point-to-point resolution of 0.20 nm.


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