Intratracheal Instillation of Exogenous Surfactant Reduces Pulmonary Hyperoxic Injury

2015 ◽  
pp. 318-320 ◽  
Author(s):  
Sadis Matalon ◽  
Bruce A. Holm
Keyword(s):  
Intratracheal Instillation ◽  
Exogenous Surfactant

scholarly journals Acute Pathophysiological Effects of Intratracheal Instillation of Budesonide and Exogenous Surfactant in a Neonatal Surfactant-depleted Piglet Model

2010 ◽  
Vol 51 (4) ◽  
pp. 219-226 ◽  
Author(s):  
Chia-Feng Yang ◽  
Mei-Jy Jeng ◽  
Wen-Jue Soong ◽  
Yu-Sheng Lee ◽  
Pen-Chen Tsao ◽  
...  
Keyword(s):  
Intratracheal Instillation ◽  
Exogenous Surfactant

Effects of surfactant distribution and ventilation strategies on efficacy of exogenous surfactant

1998 ◽  
Vol 85 (2) ◽  
pp. 676-684 ◽  
Author(s):  
Carolyn L. Kerr ◽  
Yushi Ito ◽  
Stuart E. E. Manwell ◽  
Ruud A. W. Veldhuizen ◽  
Li-Juan Yao ◽  
...  
Keyword(s):  
Intratracheal Instillation ◽  
Distribution Patterns ◽  
Exogenous Surfactant ◽  
Ventilation Strategy ◽  
Positive End Expiratory Pressure ◽  
Treatment Groups ◽  
Group 3 ◽  
Ventilation Strategies ◽  
Group 2 ◽  
Group 1

The effects of both surfactant distribution patterns and ventilation strategies utilized after surfactant administration were assessed in lung-injured adult rabbits. Animals received 50 mg/kg surfactant via intratracheal instillation in volumes of either 4 or 2 ml/kg. A subset of animals from each treatment group was euthanized for evaluation of the exogenous surfactant distribution. The remaining animals were randomized into one of three ventilatory groups: group 1 [tidal volume (Vt) of 10 ml/kg with 5 cmH2O positive end-expiratory pressure (PEEP)]; group 2(Vt of 5 ml/kg with 5 cmH2O PEEP); or group 3(Vt of 5 ml/kg with 9 cmH2O PEEP). Animals were ventilated and monitored for 3 h. Distribution of the surfactant was more uniform when it was delivered in the 4 ml/kg volume. When the distribution of surfactant was less uniform, arterial[Formula: see text] values were greater in groups 2 and 3 compared with group 1. Oxygenation differences among the different ventilation strategies were less marked in animals with the more uniform distribution pattern of surfactant (4 ml/kg). In both surfactant treatment groups, a high mortality was observed with the ventilation strategy used for group 3. We conclude that the distribution of exogenous surfactant affects the response to different ventilatory strategies in this model of acute lung injury.

scholarly journals Pulmonary Surfactant and Bacterial Lipopolysaccharide: The Interaction and its Functional Consequences

2017 ◽  
pp. S147-S157 ◽  
Author(s):  
M. KOLOMAZNIK ◽  
Z. NOVA ◽  
A. CALKOVSKA
Keyword(s):  
Lung Injury ◽  
Respiratory System ◽  
Pulmonary Surfactant ◽  
Intratracheal Instillation ◽  
Clinical Importance ◽  
Inflammatory Cells ◽  
Blood Stream ◽  
Surfactant Molecule ◽  
Exogenous Surfactant ◽  
Alveolar Type

The respiratory system is constantly exposed to pathogens which enter the lungs by inhalation or via blood stream. Lipopolysaccharide (LPS), also named endotoxin, can reach the airspaces as the major component of the outer membrane of Gram-negative bacteria, and lead to local inflammation and systemic toxicity. LPS affects alveolar type II (ATII) cells and pulmonary surfactant and although surfactant molecule has the effective protective mechanisms, excessive amount of LPS interacts with surfactant film and leads to its inactivation. From immunological point of view, surfactant specific proteins (SPs) SP-A and SP-D are best characterized, however, there is increasing evidence on the involvement of SP-B and SP-C and certain phospholipids in immune reactions. In animal models, the instillation of LPS to the respiratory system induces acute lung injury (ALI). It is of clinical importance that endotoxin-induced lung injury can be favorably influenced by intratracheal instillation of exogenous surfactant. The beneficial effect of this treatment was confirmed for both natural porcine and synthetic surfactants. It is believed that the surfactant preparations have anti-inflammatory properties through regulating cytokine production by inflammatory cells. The mechanism by which LPS interferes with ATII cells and surfactant layer, and its consequences are discussed below.

Effects of Exogenous Surfactant on Acute Lung Injury Induced by Intratracheal Instillation of Infant Formula or Human Breast Milk in Rabbits 

1999 ◽  
Vol 91 (1) ◽  
pp. 240-252 ◽  
Author(s):  
Kahoru Nishina ◽  
Katsuya Mikawa ◽  
Yumiko Takao ◽  
Nobuhiro Maekawa ◽  
Hidefumi Obara
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Infant Formula ◽  
Intratracheal Instillation ◽  
Lavage Fluid ◽  
Lung Damage ◽  
Exogenous Surfactant ◽  
Human Breast Milk ◽  
Dependent Manner ◽  
Milk Products

Background An animal experimental model of acute lung injury after intratracheal instillation of acidified milk products has been recently demonstrated. Exogenous administration of surfactant has proved to be successful treatment for acute lung injury induced by many causes including acid aspiration. The authors conducted this study to investigate whether exogenous surfactant can reduce the magnitude of lung damage induced in rabbits by acidified milk products. Methods The lung injury was induced by intratracheal instillation of acidified human breast milk or acidified infant formula (0.8 ml/kg, pH 1.8). Thirty minutes after the insult, some animals were treated with intratracheal surfactant 100 or 200 mg/kg. Lung compliance and alveolar-to-arterial oxygen gradient were recorded during ventilation. After 4 or 12 h, the lungs were excised to determine physiologic and histologic lung damage. Albumin, interleukin-8, and eicosanoids in bronchoalveolar lavage fluid and superoxide production by neutrophils were measured. Results The acidified milk products increased A-aD(O2)(550+/-52 and 156+/-28 mmHg; mean+/-SD at 4 h in saline solution and infant formula groups, respectively), lung wet-to-dry weight ratio (6.6+/-0.5 and 5.6 +/- 0.2), %neutrophils in bronchoalveolar lavage fluid (84+/-4% and 8+/-20%), and decreased compliance (0.76+/-0.09 and 1.90+/-0.11 ml/cm H2O). Surfactant improved these variables in a dose-dependent manner (A-aDO2 = 363+/-50 and 237+/-55 mmHg in 100-mg/kg and 200-mg/kg surfactant groups). Surfactant attenuated extensive histologic changes caused by the milk products. Superoxide production was less in rabbits receiving surfactant than in those not receiving it. Conclusion Exogenous surfactant improved physiologic, histologic, and biochemical lung injury induced by acidified milk products in a dose-dependent manner. The effectiveness of surfactant may be caused, in part, by inhibition of neutrophils' sequestration and activation. These data indicate that intratracheal instillation of surfactant may be a promising therapeutic modality in acute lung injury resulting from aspiration of acidified milk products.

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.

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