Intratracheal Inhalation vs Intratracheal Instillation: Differences in Particle Effects

1997 ◽  
Vol 40 (2) ◽  
pp. 220-227 ◽  
Author(s):  
M Osier
Keyword(s):  
Intratracheal Instillation

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.

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.

Bioavailability in Vivo of Benzo[a]Pyrene Adsorbed to Diesel Particulate

1991 ◽  
Vol 7 (3) ◽  
pp. 125-139 ◽  
Author(s):  
David R. Bevan ◽  
David M. Ruggio
Keyword(s):  
Health Risks ◽  
Quantitative Description ◽  
Intratracheal Instillation ◽  
Direct Analysis ◽  
Sprague Dawley ◽  
Reasonable Estimate ◽  
Diesel Particulate ◽  
Sprague Dawley Rats

To evaluate health risks associated with exposure to particulates in the environment, it is necessary to quantify the bioavailability of carcinogens associated with the particulates. Direct analysis of bioavailability in vivo is most readily accomplished by adsorbing a radiolabeled form of the carcinogen to the particulate. A sam ple of native diesel particulate collected from an Oldsmobile die sel engine that contained 1.03 μ g benzo[ a] pyrene ( BaP)/ g particulate was supplemented with exogenous [ 3 H]- BaP to pro duce a particulate containing 2.62 μ g BaP/g. To insure that elu tion of BaP from native and [3 H] -BaP-supplemented particulate was similar, in vitro analyses were performed. When using phos pholipid vesicles composed of dimyristoylphosphatidylcholine (DMPC), 1.52% of total BaP was eluted from native particulate into the vesicles in 18 hrs; from [ 3 H] -BaP supplemented particu late, 1.68% was eluted. Using toluene as eluent, 2.55% was eluted from native particulate, and 8.25% from supplemented particulate, in 6 hrs. Supplemented particulate was then instilled intratracheally into male Sprague-Dawley rats and distribution of radioactivity was analyzed at selected times over 3 days. About 50% of radioactivity remained in lungs at 3 days following instil lation, with 30% being excreted into feces and the remainder dis tributed throughout the organs of the rats. To estimate the amount of radioactivity that entered feces through swallowing of a portion of the instilled dose, [3 H] -BaP-supplemented particu late was instilled intratracheally into rats that had a cannula sur gically implanted in the bile duct. Rate of elimination of radio activity into bile was monitored; 10.6% of radioactivity was re covered in 6 hr, an amount slightly lower than the 12.8% ex creted in 6 hrs into feces of animals with intact bile ducts. Our studies provide a quantitative description of the distribution of BaP and its metabolites following intratracheal instillation of diesel particulate. Because rates of elution of BaP in vitro are similar for native diesel particulate and particulate with supple mental [ 3H] -BaP, our results provide a reasonable estimate of the bioavailability in vivo of BaP associated with diesel particu late.

Increased susceptibility of purinergic receptor-deficient mice to lung infection withPseudomonasaeruginosa

2005 ◽  
Vol 289 (5) ◽  
pp. L890-L895 ◽  
Author(s):  
Cara Geary ◽  
Henry Akinbi ◽  
Tom Korfhagen ◽  
Jean-Etienne Fabre ◽  
Richard Boucher ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Purinergic Receptors ◽  
Tissue Injury ◽  
Purinergic Receptor ◽  
Intratracheal Instillation ◽  
Lavage Fluid ◽  
Sublethal Dose ◽  
Wild Type ◽  
Double Knockout

Purinergic receptors are expressed throughout the respiratory system in diverse cell types. The efficiency of mucus clearance in the airways, the cascade leading to tissue injury, and inflammation are modulated by autocrine/paracrine release of nucleotides and signaling by purinergic receptors. We assessed the role of purinergic receptors in innate host defense of the lung in vivo by infecting mice deficient in P2Y1, P2Y2, or both receptors with intratracheal instillation of Pseudomonas aeruginosa. After P. aeruginosa challenge, all double knockout (P2Y1/P2Y2−/−) mice succumbed within 30 h of challenge, whereas 85% of the wild-type mice survived. Thirty-three percent of wild-type mice survived beyond 96 h. Single knockout mice, P2Y1−/−, or P2Y2−/−, exhibited intermediate survivals. Twenty-four hours following intratracheal instillation of a sublethal dose of P. aeruginosa, the level of total protein in bronchoalveolar lavage fluid was 1.8-fold higher in double knockout than in wild-type mice ( P < 0.04). Total cell count in bronchoalveolar lavage fluids at 4 h and levels of IL-6 and macrophage inflammatory protein-2 in lung homogenates at 24 h postchallenge were significantly reduced in P2Y1/P2Y2−/− mice relative to wild-type mice. These findings suggest that purinergic receptors exert a protective role against infection of the lungs by P. aeruginosa by decreasing protein leak and enhancing proinflammatory cytokine response.

Lung toxicity induced by intratracheal instillation of size-fractionated tire particles

2009 ◽  
Vol 189 (3) ◽  
pp. 206-214 ◽  
Author(s):  
Paride Mantecca ◽  
Giulio Sancini ◽  
Elisa Moschini ◽  
Francesca Farina ◽  
Maurizio Gualtieri ◽  
...  
Keyword(s):  
Intratracheal Instillation ◽  
Lung Toxicity

scholarly journals Pulmonary toxicity screening of triclosan in rats after intratracheal instillation

2013 ◽  
Vol 38 (3) ◽  
pp. 471-475 ◽  
Author(s):  
Jung-Taek Kwon ◽  
Young-Su Yang ◽  
Min-Sung Kang ◽  
Gyun-Baek Seo ◽  
Dong Hun Lee ◽  
...  
Keyword(s):  
Pulmonary Toxicity ◽  
Intratracheal Instillation ◽  
Toxicity Screening
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