scholarly journals Systemic Immunoresponses in Mice after Repeated Exposure of Lungs to Spores of Streptomyces californicus

2003 ◽  
Vol 10 (1) ◽  
pp. 30-37 ◽  
Author(s):  
J. Jussila ◽  
J. Pelkonen ◽  
V.-M. Kosma ◽  
J. Mäki-Paakkanen ◽  
H. Komulainen ◽  
...  
Keyword(s):  
Indoor Air ◽  
Bronchoalveolar Lavage Fluid ◽  
Inflammatory Cell ◽  
Intratracheal Instillation ◽  
Lavage Fluid ◽  
Chemotherapeutic Agents ◽  
Repeated Exposure ◽  
Adverse Health Effects ◽  
Dose Levels ◽  
Dose Dependent

ABSTRACT Microbial growth in moisture-damaged buildings is associated with respiratory and other symptoms in the occupants. Streptomyces spp. are frequently isolated from such buildings. In the present study, we evaluated the responses of mice after repeated exposure to spores of Streptomyces californicus. Mice were exposed via intratracheal instillation to six doses (at 7-day intervals) of the spores of S. californicus, originally isolated from the indoor air of a moisture-damaged building, at three dose levels (2 × 103, 2 × 105, and 2 × 107 spores). Inflammation and toxicity, including changes in cell populations in the lungs, lymph nodes, and spleen, were evaluated 24 h after the last dosage. The exposure provoked a dose-dependent inflammatory cell response, as detected by the intense recruitment of neutrophils, but the numbers of macrophages and lymphocytes in the airways also increased. The cellular responses corresponded to the dose-dependent increases in inflammation- and cytotoxicity-associated biochemical markers (i.e., levels of albumin, total protein, and lactate dehydrogenase) in bronchoalveolar lavage fluid. The spore exposure increased the number of both activated and nonactivated T lymphocytes. Also, the amounts of CD3− CD4− and unconventional CD3− CD4+ lymphocytes in the lung tissue were augmented. Interestingly, the spore exposure decreased cells in the spleen. This effect was strongest at the dose of 2 × 105 spores. These results indicate that the spores of S. californicus are capable of provoking both immunostimulation in lungs (inflammation) and systemic immunotoxicity, especially in the spleen. The immunotoxic effect resembled that caused by chemotherapeutic agents, originally isolated from Streptomyces spp. Thus, S. californicus must be considered a microbial species with potential to cause systemic adverse health effects in occupants of moisture-damaged buildings.

PAMP is a novel inhibitor of the tachykinin release in the airway of guinea pigs

1997 ◽  
Vol 272 (6) ◽  
pp. L1066-L1069
Author(s):  
H. Kanazawa ◽  
H. Kamoi ◽  
T. Kawaguchi ◽  
S. Shoji ◽  
T. Fujii ◽  
...  
Keyword(s):  
Substance P ◽  
Bronchoalveolar Lavage ◽  
Guinea Pigs ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Neurokinin A ◽  
Dependent Manner ◽  
C Fiber ◽  
Dose Dependent

Proadrenomedullin NH2-terminal 20 peptide (PAMP), a newly identified hypotensive peptide, may play physiological roles in airway and cardiovascular controls. This study was designed to determine the mechanism responsible for the bronchoprotective effects of PAMP on capsaicin-induced bron-choconstriction in anesthetized guinea pigs. PAMP (10(-8)-10(-6) M) significantly inhibited capsaicin-induced bronchoconstriction in a dose-dependent manner. The bronchoprotective effect of PAMP (10(-6) M) was as large as that of isoproterenol (10(-7) M) and lasted > 10 min. The concentration of immunoreactive substance P (SP) in bronchoalveolar lavage fluid after administration of capsaicin (4 x 10(-6) M) was 120 +/- 10 fmol/ml. PAMP significantly inhibited the release of immunoreactive SP in a dose-dependent manner (60 +/- 6 fmol/ml for (10(-6) M PAMP, P < 0.01; 84 +/- 6 fmol/ml for 10(-7) M PAMP, P < 0.01; and 95 +/- 6 fmol/ml for 10(-8) M PAMP, P < 0.05). PAMP (10(-6) M) did not significantly affect exogenous neurokinin A (NKA) or NKA + SP-induced bronchoconstriction, whereas isoproterenol (10(-7) M) significantly inhibited exogenous tachykinin-induced bronchoconstriction. These findings suggest that the bronchoprotective effects of PAMP are mainly due to inhibition of the release of tachykinins at airway C-fiber endings.

scholarly journals Therapeutic Effect of Dipsacus asperoides C. Y. Cheng et T. M. Ai in Ovalbumin-Induced Murine Model of Asthma

2019 ◽  
Vol 20 (8) ◽  
pp. 1855 ◽  
Author(s):  
Na-Rae Shin ◽  
A Yeong Lee ◽  
Gunhyuk Park ◽  
Je-Won Ko ◽  
Jong-Choon Kim ◽  
...  
Keyword(s):  
Immune Responses ◽  
Allergic Asthma ◽  
Bronchoalveolar Lavage Fluid ◽  
Inflammatory Cell ◽  
Lavage Fluid ◽  
Suppressive Effect ◽  
Oral Gavage ◽  
Asthma Model ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Dipsacus asperoides C. Y. Cheng et T. M. Ai (DA) has been used in China as a traditional medicine to treat lumbar and knee pain, liver dysfunction, and fractures. We explored the suppressive effect of DA on allergic asthma using an ovalbumin (OVA)-induced asthma model. In the asthma model, female Balb/c mice were sensitized to OVA on day 0 and 14 to boost immune responses and then exposed to OVA solution by using an ultrasonic nebulizer on days 21 to 23. DA (20 and 40 mg/kg) was administered to mice by oral gavage on days 18 to 23. Methacholine responsiveness was determined on day 24 using a plethysmography. On day 25, we collected bronchoalveolar lavage fluid, serum, and lung tissue from animals under anesthesia. DA treatment effectively inhibited methacholine responsiveness, inflammatory cell infiltration, proinflammatory cytokines such as interleukin (IL)-5 and IL-13, and immunoglobulin (Ig) E in OVA-induced asthma model. Reductions in airway inflammation and mucus hypersecretion, accompanied by decreases in the expression of inducible nitric oxide synthase (iNOS) and the phosphorylation of nuclear factor kappa B (NF-κB), were also observed. Our results indicated that DA attenuated the asthmatic response, and that this attenuation was closely linked to NF-κB suppression. Thus, this study suggests that DA is a potential therapeutic for allergic asthma.

Leukotrienes mediate part of Ova-induced lung effects in mice via EGFR

2003 ◽  
Vol 285 (4) ◽  
pp. L808-L818 ◽  
Author(s):  
B. Boris Vargaftig ◽  
Monique Singer
Keyword(s):  
Bronchoalveolar Lavage Fluid ◽  
Egf Receptor ◽  
Kinase Inhibitor ◽  
Airway Remodeling ◽  
Intratracheal Instillation ◽  
Lavage Fluid ◽  
Egfr Tyrosine Kinase Inhibitor ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Cysteinyl Leukotriene

Antigen induces murine bronchial hyperreactivity (BHR), inflammation, mucus accumulation, and airway remodeling. To investigate whether leukotrienes (LT) mediate the effects of antigen [ovalbumin (Ova)], we studied 5-lipoxygenase (5-LO) expression in immunized BP2 mice and blocked LT synthesis with the 5-LO inhibitor zileuton or antagonized their effects with receptor antagonists [cysteinyl leukotriene (Cys-LT)-ra MK-571, LY-171883; LTB4-ra PH-163]. Cys-LT content increased in the bronchoalveolar lavage fluid (BALF) as early as 15 min after the intratracheal instillation of Ova. Zileuton inhibited LT release in the BALF and eosinophil recruitment in the lungs, and dose dependently reduced BHR, mucus accumulation, and remodeling, as did the LT-ra. Thus LT, released just after antigen challenge, might constitute the first step in accounting for the effects of Ova. Because mucus accumulation is regulated via the EGF receptor (EGFR), which is also implicated in the effects of LT, we studied this pathway with AG-1478, an EGFR tyrosine kinase inhibitor given at 0.5, 4, and 20 mg/kg. AG-1478 inhibited BHR, inflammation, and lung remodeling induced by Ova or by molecules themselves generated by Ova, such as LT, IL-13, and monocyte chemoattractant protein-1, which promote identical effects, suggesting the involvement of the EGFR pathway in the asthma-like syndrome observed.

scholarly journals S1PR2 Inhibition Attenuates Allergic Asthma Possibly by Regulating Autophagy

2021 ◽  
Vol 11 ◽  
Author(s):  
Hanye Liu ◽  
Liangchang Li ◽  
Zhengai Chen ◽  
Yilan Song ◽  
Weidong Liu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Expression ◽  
Bronchoalveolar Lavage Fluid ◽  
Inflammatory Cell ◽  
Airway Remodeling ◽  
Lavage Fluid ◽  
Expression Levels ◽  
Sphingosine 1 Phosphate ◽  
Masson Staining

This study is to investigate the role of Sphingosine-1-phosphate (S1P) in the asthma progression, and the involvement of autophagy. Airway remodeling mice were subjected to the HE, PAS, and Masson staining. Protein expression levels in the tissues, samples and model cells were detected with ELISA, Western blot analysis, and immunohistochemical/immunofluorescent analysis. The S1P2 receptor antagonist JTE-013 decreased the inflammatory cell infiltration and goblet cell production in asthmatic mice tissues. The IL-1, IL-4, IL-5 and serum IgE contents were decreased in bronchoalveolar lavage fluid, while the Beclin1 expression in lung tissues was decreased. The LC3B1 to LC-3B2 conversion was decreased, with increased P62 accumulation and decreased p-P62 expression. In airway remodeling mice, JTE-013 significantly decreased collagen deposition in lung tissues and decreased smooth muscle cell smooth muscle activating protein expression. In lung tissue, the expression levels of Beclin1 were decreased, with decreased LC3B1 to LC-3B2 conversion, as well as the increased P62 accumulation and decreased p-P62 expression. However, these effects were reversed by the RAC1 inhibitor EHT 1864. Similar results were observed for the silencing of S1P2 receptor in the cells, as shown by the decreased Beclin1 expression, decreased LC3B1 to LC-3B2 conversion, increased P62 accumulation, and decreased p-P62 expression. The smooth muscle activators were significantly decreased in the JTE-013 and EHT1864 groups, and the EHT 1864 + S1P2-SiRNA expression level was increased. S1P is involved in the progression of asthma and airway remodeling, which may be related to the activation of S1PR2 receptor and inhibition of autophagy through RAC1.

scholarly journals Anti-inflammatory Activity of Lefamulin in a Lipopolysaccharide-Induced Lung Neutrophilia Model

2020 ◽  
Author(s):  
Michael Hafner ◽  
Susanne Paukner ◽  
Wolfgang W. Wicha ◽  
Boška Hrvačić ◽  
Steven P. Gelone
Keyword(s):  
Bacterial Pneumonia ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Inflammatory Activity ◽  
Free Base ◽  
Cell Counts ◽  
Oral Dexamethasone ◽  
Anti Inflammatory ◽  
Dose Dependent ◽  
Neutrophil Cell

ABSTRACTLefamulin is a novel pleuromutilin antibiotic approved for the treatment of community-acquired bacterial pneumonia. This study demonstrated anti-inflammatory activity of lefamulin in a murine lipopolysaccharide-induced lung neutrophilia model. Pretreatment of mice at clinically relevant lefamulin subcutaneous doses (35, 70, 140 mg/kg [free base]) followed by intranasal lipopolysaccharide challenge (5 μg/50 μL/mouse) demonstrated significant, dose-dependent reductions in total and neutrophil cell counts in bronchoalveolar lavage fluid samples, with reductions comparable to oral dexamethasone (0.5 mg/kg) pretreatment.

scholarly journals The Fermented Soy Product ImmuBalanceTM Suppresses Airway Inflammation in a Murine Model of Asthma

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3380
Author(s):  
Hideaki Kadotani ◽  
Kazuhisa Asai ◽  
Atsushi Miyamoto ◽  
Kohei Iwasaki ◽  
Takahiro Kawai ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Airway Inflammation ◽  
Murine Model ◽  
Bronchoalveolar Lavage Fluid ◽  
Inflammatory Cell ◽  
Allergic Airway Inflammation ◽  
Lavage Fluid ◽  
Cell Infiltration ◽  
Mucus Production ◽  
Cell Counts

The fermented soy product ImmuBalance contains many active ingredients and its beneficial effects on some allergic diseases have been reported. We hypothesized that ImmuBalance could have potential effects on airway inflammation in a murine model of asthma. Mice sensitized and challenged with ovalbumin developed airway inflammation. Bronchoalveolar lavage fluid was assessed for inflammatory cell counts and levels of cytokines. Lung tissues were examined for cell infiltration and mucus hypersecretion. Oral administration of ImmuBalance significantly inhibited ovalbumin-induced eosinophilic inflammation and decreased Th2 cytokine levels in bronchoalveolar lavage fluid (p < 0.05). In addition, lung histological analysis showed that ImmuBalance inhibited inflammatory cell infiltration and airway mucus production. Our findings suggest that supplementation with ImmuBalance may provide a novel strategy for the prevention or treatment of allergic airway inflammation.

scholarly journals Active vs. sedentary lifestyle from weaning to adulthood and susceptibility to ozone in rats

2017 ◽  
Vol 312 (1) ◽  
pp. L100-L109 ◽  
Author(s):  
C. J. Gordon ◽  
P. M. Phillips ◽  
A. Ledbetter ◽  
S. J. Snow ◽  
M. C. Schladweiler ◽  
...  
Keyword(s):  
Air Pollutants ◽  
Bronchoalveolar Lavage Fluid ◽  
Sedentary Lifestyle ◽  
Lavage Fluid ◽  
Whole Body ◽  
Chronic Exercise ◽  
Adverse Health Effects ◽  
Long Evans ◽  
Balf Cell ◽  
Tolerance Testing

The prevalence of a sedentary (SED) life style combined with calorically rich diets has spurred the rise in childhood obesity, which, in turn, translates to adverse health effects in adulthood. Obesity and lack of active (ACT) lifestyle may increase susceptibility to air pollutants. We housed 22-day-old female Long-Evans rats in a cage without (SED) or with a running wheel (ACT). After 10 wk the rats ran 310 ± 16.3 km. Responses of SED and ACT rats to whole-body O3 (0, 0.25, 0.5, or 1.0 ppm; 5 h/day for 2 days) was assessed. Glucose tolerance testing (GTT) was performed following the first day of O3. ACT rats had less body fat and an improved glucose GTT. Ventilatory function (plethysmography) of SED and ACT groups was similarly impaired by O3. Bronchoalveolar lavage fluid (BALF) was collected after the second O3 exposure. SED and ACT rats were hyperglycemic following 1.0 ppm O3. GTT was impaired by O3 in both groups; however, ACT rats exhibited improved recovery to 0.25 and 1.0 ppm O3. BALF cell neutrophils and total cells were similarly increased in ACT and SED groups exposed to 1.0 ppm O3. O3-induced increase in eosinophils was exacerbated in SED rats. Chronic exercise from postweaning to adulthood improved some of the metabolic and pulmonary responses to O3 (GTT and eosinophils) but several other parameters were unaffected. The reduction in O3-induced rise in BALF eosinophils in ACT rats suggests a possible link between a SED lifestyle and incidence of asthma-related symptoms from O3.

scholarly journals Assessment of Cytokine-Induced Neutrophil Chemoattractants as Biomarkers for Prediction of Pulmonary Toxicity of Nanomaterials

Nanomaterials ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1563
Author(s):  
Taisuke Tomonaga ◽  
Hiroto Izumi ◽  
Takako Oyabu ◽  
Byeong-Woo Lee ◽  
Masaru Kubo ◽  
...  
Keyword(s):  
Pulmonary Toxicity ◽  
Inhalation Exposure ◽  
Intratracheal Instillation ◽  
Lavage Fluid ◽  
Dependent Manner ◽  
High Toxicity ◽  
Operating Characteristics ◽  
Low Toxicity ◽  
Titanium Dioxides ◽  
Dose Dependent

This work determines whether cytokine-induced neutrophil chemoattractants (CINC)-1, CINC-2 and CINC-3 can be markers for predicting high or low pulmonary toxicity of nanomaterials (NMs). We classified NMs of nickel oxide (NiO) and cerium dioxide (CeO2) into high toxicity and NMs of two types of titanium dioxides (TiO2 (P90 and rutile)) and zinc oxide (ZnO) into low toxicity, and we analyzed previous data of CINCs in bronchoalveolar lavage fluid (BALF) of rats from three days to six months after intratracheal instillation (0.2 and 1.0 mg) and inhalation exposure (0.32–10.4 mg/m3) of materials (NiO, CeO2, TiO2 (P90 and rutile), ZnO NMs and micron-particles of crystalline silica (SiO2)). The concentration of CINC-1 and CINC-2 in BALF had different increase tendency between high and low pulmonary toxicity of NMs and correlated with the other inflammatory markers in BALF. However, CINC-3 increased only slightly in a dose-dependent manner compared with CINC-1 and CINC-2. Analysis of receiver operating characteristics for the toxicity of NMs by CINC-1 and CINC-2 showed the most accuracy of discrimination of the toxicity at one week or one month after exposure and CINC-1 and CINC-2 in BALF following intratracheal instillation of SiO2 as a high toxicity could accurately predict the toxicity at more than one month after exposure. These data suggest that CINC-1 and CINC-2 may be useful biomarkers for the prediction of pulmonary toxicity of NMs relatively early in both intratracheal instillation and inhalation exposure.

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