scholarly journals The M2a Macrophage Phenotype Accompanies Pulmonary Granuloma Resolution in Mmp12 Knock-Out Mice Instilled with Multiwall Carbon Nanotubes

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.

2021 ◽  
Vol 22 (7) ◽  
pp. 3705
Author(s):  
Barbara P. Barna ◽  
Anagha Malur ◽  
Mary Jane Thomassen

Poorly soluble environmental antigens, including carbon pollutants, are thought to play a role in the incidence of human sarcoidosis, a chronic inflammatory granulomatous disease of unknown causation. Currently, engineered carbon products such as multiwall carbon nanotubes (MWCNT) are manufactured commercially and have been shown to elicit acute and chronic inflammatory responses in experimental animals, including the production of granulomas or fibrosis. Several years ago, we hypothesized that constructing an experimental model of chronic granulomatosis resembling that associated with sarcoidosis might be achieved by oropharyngeal instillation of MWCNT into mice. This review summarizes the results of our efforts to define mechanisms of granuloma formation and identify potential therapeutic targets for sarcoidosis. Evidence is presented linking findings from the murine MWCNT granuloma model to sarcoidosis pathophysiology. As our goal was to determine what pulmonary inflammatory pathways might be involved, we utilized mice of knock-out (KO) backgrounds which corresponded to deficiencies noted in sarcoidosis patients. A primary example of this approach was to study mice with a myeloid-specific knock-out of the lipid-regulated transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ) which is strikingly depressed in sarcoidosis. Among the major findings associated with PPARγ KO mice compared to wild-type were: (1) exacerbation of granulomatous and fibrotic histopathology in response to MWCNT; (2) elevation of inflammatory mediators; and (3) pulmonary retention of a potentially antigenic ESAT-6 peptide co-instilled with MWCNT. In line with these data, we also observed that activation of PPARγ in wild-type mice by the PPARγ-specific ligand, rosiglitazone, significantly reduced both pulmonary granuloma and inflammatory mediator production. Similarly, recognition of a deficiency of ATP-binding cassette (ABC) lipid transporter ABCG1 in sarcoidosis led us to study MWCNT instillation in myeloid-specific ABCG1 KO mice. As anticipated, ABCG1 deficiency was associated with larger granulomas and increased levels of inflammatory mediators. Finally, a transcriptional survey of alveolar macrophages from MWCNT-instilled wild-type mice and human sarcoidosis patients revealed several common themes. One of the most prominent mediators identified in both human and mouse transcriptomic analyses was MMP12. Studies with MMP12 KO mice revealed similar acute reactions to those in wild-type but at chronic time points where wild-type maintained granulomatous disease, resolution occurred with MMP12 KO mice suggesting MMP12 is necessary for granuloma progression. In conclusion, these studies suggest that the MWCNT granuloma model has relevance to human sarcoidosis study, particularly with respect to immune-specific pathways.


2018 ◽  
Author(s):  
Gen Hayase

By exploiting the dispersibility and rigidity of boehmite nanofibers (BNFs) with a high aspect ratio of 4 nm in diameter and several micrometers in length, multiwall-carbon nanotubes (MWCNTs) were successfully dispersed in aqueous solutions. In these sols, the MWCNTs were dispersed at a ratio of about 5–8% relative to BNFs. Self-standing BNF–nanotube films were also obtained by filtering these dispersions and showing their functionality. These films can be expected to be applied to sensing materials.


2016 ◽  
Vol 25 (4) ◽  
pp. 459-464 ◽  
Author(s):  
M.I. Abduo ◽  
A.S. Dahab ◽  
Hesham Abuseda ◽  
Abdulaziz M. AbdulAziz ◽  
M.S. Elhossieny

2021 ◽  
Vol 4 (3) ◽  
pp. 2345-2350
Author(s):  
Chaofeng Wang ◽  
Yi Hao ◽  
Yue Wang ◽  
Huijia Song ◽  
Sameer Hussain ◽  
...  

2015 ◽  
Vol 1782 ◽  
pp. 1-8
Author(s):  
Ning-Qin Deng ◽  
He Tian ◽  
Qing-Tang Xue ◽  
Zhe Wang ◽  
Hai-Ming Zhao ◽  
...  

ABSTRACTNanogenerators (NGs) have great potential to solve the problems of energy depletion and environmental pollution. Here, two types of flexible nanogenerators (FNGs) based on graphene oxide (GO) and multiwall carbon nanotubes (MW-CNTs) are presented. The peak output voltage and current of GO based FNG reached up to 2 V and 30 nA, respectively, under 15 N force at 1 Hz. Moreover, the output voltage could be improved to 34.4 V when the frequency was increased to 10 Hz. It was also found the output voltage increased from 0.1 V to 2.0 V using a released GO structure. The other FNG was made by MW-CNTs mixed with ZnO nanoparticles (NPs). Its output voltage and power reached up to 7.5 V and 18.75 mW, respectively, which is much larger than that of bare ZnO based FNG. Furthermore, a peak voltage of 30 V could be gained by stamping one’s foot on the FNG. Finally, a modified NG was fabricated using four springs and two flexible layers. As a result, the voltage and power reached up to 9 V and 27mW, respectively. These works may bring out broad applications in energy harvesting.


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