Standardization of Intratracheal Instillation Study of Manufactured Nanomaterials

2019 ◽  
pp. 107-122 ◽  
Author(s):  
Toshio Kobayashi ◽  
Yutaka Oshima ◽  
Yasuhiro Tsubokura ◽  
Takakazu Kayashima ◽  
Makoto Nakai ◽  
...  
Keyword(s):  
Intratracheal Instillation ◽  
Manufactured Nanomaterials

scholarly journals Comparison of Data between Intratracheal Instillation and Inhalation Studies for Estimation of Harmful Effects of Manufactured Nanomaterials

2013 ◽  
Vol 68 (3) ◽  
pp. 161-167 ◽  
Author(s):  
Yasuo MORIMOTO ◽  
Masanori HORIE ◽  
Schinichi KITAJIMA ◽  
Shoji FUKUSHIMA ◽  
Toru TAKEBAYASHI
Keyword(s):  
Intratracheal Instillation ◽  
Manufactured Nanomaterials ◽  
Harmful Effects

Reactivity of Pulmonary Alveolar Cells to Crocidolite Asbestos Fibers

1982 ◽  
Vol 40 ◽  
pp. 334-335
Author(s):  
Charles L. Sanders ◽  
Roy R. Adee
Keyword(s):  
Osmium Tetroxide ◽  
Intratracheal Instillation ◽  
Uranyl Acetate ◽  
Fiber Suspension ◽  
Nacl Solution ◽  
Alveolar Cells ◽  
Asbestos Fibers ◽  
Fischer Rats ◽  
Mineral Silicates

Asbestos is a generic name for a group of hydrated mineral silicates that occur naturally in a fibrous form. The early interactions of asbestos fibers with alveolar cells in large part determines their long-term toxicity. Young adult, SPF, Fischer rats were given a single intratracheal instillation of 2 mg crocidolite asbestos suspended in 0.5 ml of 0.9% NaCl solution. About 80% of the fibers had lengths of less than 10 ym as measured on light micrographs of the fiber suspension. Two rats were killed at 3 hr, 1 d and 1, 4, 8, 12 and 16 wk after instillation and the lungs instilled with 8 ml McDowell - Trumps at 20 cm H2O. Lung tissue was dehydrated and sputtered coated with palladium-gold for SEM or post-fixed in osmium tetroxide, embedded in epoxy resin and sections stained with uranyl acetate and lead citrate for TEM.

Ultrastructure of rat alveolar macrophages activated in situ by poly:IC

1987 ◽  
Vol 45 ◽  
pp. 768-769
Author(s):  
A. M. Klinkner ◽  
R. A. Weiss ◽  
A. Kelley ◽  
P. J. Bugelski
Keyword(s):  
Venous Blood ◽  
Intratracheal Instillation ◽  
Buffy Coat ◽  
Fischer 344 Rats ◽  
Blood Monocytes ◽  
Fischer 344 ◽  
Polyinosinic:Polycytidylic Acid ◽  
Macrophage Activator ◽  
Endogenous Peroxidase

Polyinosinic:polycytidylic acid is an inducer of interferon and a macrophage activator. We have found that intratracheal instillation of polyI:C (IT-pI:C) activates rat bronchoalveolar lavage cells (BAL) for a variety of functions. Examination of Giemsa stained, cytocentrifuge preparations showed that IT-pI:C induced a population of BAL not seen in resident BAL. The morphology of these cells suggested that they might be derived from blood monocytes. To test this hypothesis we have examined several populations of macrophages that had been stained for endogenous peroxidase activity as a marker of cells derived from the monocyte-macrophage lineage.Macrophages were obtained from Fischer 344 rats. Peritoneal exudate cells (PEC) were collected by lavage 4 days after i.p. injection of 20 ml 3% thioglycolate. Buffy coat monocytes were separated from venous blood from naive rats.

Research progress on toxicity of manufactured nanomaterials to aquatic organisms

2013 ◽  
Vol 20 (4) ◽  
pp. 902-909
Author(s):  
Lin YANG ◽  
Hengyi XU ◽  
Meng YANG ◽  
Yonghua XIONG ◽  
Xiaolin HUANG
Keyword(s):  
Aquatic Organisms ◽  
Research Progress ◽  
Manufactured Nanomaterials

scholarly journals Loss of IL-33 enhances elastase-induced and cigarette smoke extract-induced emphysema in mice

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Daisuke Morichika ◽  
Akihiko Taniguchi ◽  
Naohiro Oda ◽  
Utako Fujii ◽  
Satoru Senoo ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Intratracheal Instillation ◽  
Inflammatory Cells ◽  
Cigarette Smoke Extract ◽  
Lymphoid Cells ◽  
Chronic Obstructive ◽  
Porcine Pancreas ◽  
Obstructive Pulmonary Disease ◽  
Quantitative Morphometry ◽  
Cytokines And Chemokines

Abstract Background IL-33, which is known to induce type 2 immune responses via group 2 innate lymphoid cells, has been reported to contribute to neutrophilic airway inflammation in chronic obstructive pulmonary disease. However, its role in the pathogenesis of emphysema remains unclear. Methods We determined the role of interleukin (IL)-33 in the development of emphysema using porcine pancreas elastase (PPE) and cigarette smoke extract (CSE) in mice. First, IL-33−/− mice and wild-type (WT) mice were given PPE intratracheally. The numbers of inflammatory cells, and the levels of cytokines and chemokines in the bronchoalveolar lavage (BAL) fluid and lung homogenates, were analyzed; quantitative morphometry of lung sections was also performed. Second, mice received CSE by intratracheal instillation. Quantitative morphometry of lung sections was then performed again. Results Intratracheal instillation of PPE induced emphysematous changes and increased IL-33 levels in the lungs. Compared to WT mice, IL-33−/− mice showed significantly greater PPE-induced emphysematous changes. No differences were observed between IL-33−/− and WT mice in the numbers of macrophages or neutrophils in BAL fluid. The levels of hepatocyte growth factor were lower in the BAL fluid of PPE-treated IL-33−/− mice than WT mice. IL-33−/− mice also showed significantly greater emphysematous changes in the lungs, compared to WT mice, following intratracheal instillation of CSE. Conclusion These observations suggest that loss of IL-33 promotes the development of emphysema and may be potentially harmful to patients with COPD.

scholarly journals Size and surface modification of silica nanoparticles affect the severity of lung toxicity by modulating endosomal ROS generation in macrophages

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Masahide Inoue ◽  
Koji Sakamoto ◽  
Atsushi Suzuki ◽  
Shinya Nakai ◽  
Akira Ando ◽  
...  
Keyword(s):  
Immune Response ◽  
Surface Modification ◽  
Lung Injury ◽  
Cellular Uptake ◽  
Intratracheal Instillation ◽  
Chemical Properties ◽  
Raw264.7 Cells ◽  
Neutrophilic Infiltration ◽  
Silica Nanomaterials ◽  
Physico Chemical

Abstract Background As the application of silica nanomaterials continues to expand, increasing chances of its exposure to the human body and potential harm are anticipated. Although the toxicity of silica nanomaterials is assumed to be affected by their physio-chemical properties, including size and surface functionalization, its molecular mechanisms remain unclear. We hypothesized that analysis of intracellular localization of the particles and subsequent intracellular signaling could reveal a novel determinant of inflammatory response against silica particles with different physico-chemical properties. Results We employed a murine intratracheal instillation model of amorphous silica nanoparticles (NPs) exposure to compare their in vivo toxicities in the respiratory system. Pristine silica-NPs of 50 nm diameters (50 nm-plain) induced airway-centered lung injury with marked neutrophilic infiltration. By contrast, instillation of pristine silica particles of a larger diameter (3 μm; 3 μm-plain) significantly reduced the severity of lung injury and neutrophilic infiltration, possibly through attenuated induction of neutrophil chemotactic chemokines including MIP2. Ex vivo analysis of alveolar macrophages as well as in vitro assessment using RAW264.7 cells revealed a remarkably lower cellular uptake of 3 μm-plain particles compared with 50 nm-plain, which is assumed to be the underlying mechanism of attenuated immune response. The severity of lung injury and neutrophilic infiltration was also significantly reduced after intratracheal instillation of silica NPs with an amine surface modification (50 nm-NH2) when compared with 50 nm-plain. Despite unchanged efficacy in cellular uptake, treatment with 50 nm-NH2 induced a significantly attenuated immune response in RAW264.7 cells. Assessment of intracellular redox signaling revealed increased reactive oxygen species (ROS) in endosomal compartments of RAW264.7 cells treated with 50 nm-plain when compared with vehicle-treated control. In contrast, augmentation of endosomal ROS signals in cells treated with 50 nm-NH2 was significantly lower. Moreover, selective inhibition of NADPH oxidase 2 (NOX2) was sufficient to inhibit endosomal ROS bursts and induction of chemokine expressions in cells treated with silica NPs, suggesting the central role of endosomal ROS generated by NOX2 in the regulation of the inflammatory response in macrophages that endocytosed silica NPs. Conclusions Our murine model suggested that the pulmonary toxicity of silica NPs depended on their physico-chemical properties through distinct mechanisms. Cellular uptake of larger particles by macrophages decreased, while surface amine modification modulated endosomal ROS signaling via NOX2, both of which are assumed to be involved in mitigating immune response in macrophages and resulting lung injury.

scholarly journals Elucidation of the Molecular Pathways Involved in the Protective Effects of AUY-922 in LPS-Induced Inflammation in Mouse Lungs

2021 ◽  
Vol 14 (6) ◽  
pp. 522
Author(s):  
Mohammad S. Akhter ◽  
Mohammad A. Uddin ◽  
Khadeja-Tul Kubra ◽  
Nektarios Barabutis
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Intratracheal Instillation ◽  
Hsp90 Inhibitor ◽  
Molecular Pathways ◽  
Protective Effects ◽  
Inflammatory Pathways ◽  
Cytokines And Chemokines ◽  
The Unfolded Protein Response ◽  
Mouse Lungs

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) cause thousands of deaths every year and are associated with high mortality rates (~40%) due to the lack of efficient therapies. Understanding the molecular mechanisms associated with those diseases will most probably lead to novel therapeutics. In the present study, we investigated the effects of the Hsp90 inhibitor AUY-922 in the major inflammatory pathways of mouse lungs. Mice were treated with LPS (1.6 mg/kg) via intratracheal instillation for 24 h and were then post-treated intraperitoneally with AUY-922 (10 mg/kg). The animals were examined 48 h after AUY-922 injection. LPS activated the TLR4-mediated signaling pathways, which in turn induced the release of different inflammatory cytokines and chemokines. AUY-922 suppressed the LPS-induced inflammation by inhibiting major pro-inflammatory pathways (e.g., JAK2/STAT3, MAPKs), and downregulated the IL-1β, IL-6, MCP-1 and TNFα. The expression levels of the redox regulator APE1/Ref1, as well as the DNA-damage inducible kinases ATM and ATR, were also increased after LPS treatment. Those effects were counteracted by AUY-922. Interestingly, this Hsp90 inhibitor abolished the LPS-induced pIRE1α suppression, a major component of the unfolded protein response. Our study elucidates the molecular pathways involved in the progression of murine inflammation and supports our efforts on the development of new therapeutics against lung inflammatory diseases and sepsis.

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