Acute transient SO2-induced airway hyperreactivity: effects of nedocromil sodium

1988 ◽  
Vol 65 (3) ◽  
pp. 1119-1124 ◽  
Author(s):  
D. M. Jackson ◽  
R. P. Eady

The effect of nedocromil sodium given as an aerosol on the immediate lung hyperreactivity and lung inflammation caused by a 2-h exposure to 400 ppm SO2 has been studied in dogs. Exposure to SO2 caused an immediate increase in bronchial responsiveness to histamine aerosol that lasted for approximately 2 h. The total number of cells recovered by bronchial lavage increased postexposure. Initially this increase was caused by epithelial cells (0.25 and 1 h) and later by neutrophils (1, 2, 3, and 4 h). There was no significant change in the numbers of lymphocytes, macrophages, eosinophils, goblet cells, or mast cells in the lavages. Nedocromil sodium (approximately 8 mg) given as a nebulized aerosol before and after SO2 exposure prevented the increase in lung reactivity and attenuated the increase in the total number of cells (epithelial cells and neutrophils) in the lung lavages for the 4 h after exposure. Nedocromil sodium did not affect the reactivity of normal dogs to histamine aerosol. Nedocromil sodium appears to act as an anti-inflammatory agent in this model of lung inflammation, preventing an increase in lung reactivity and reducing cell infiltration. The mechanism of action of nedocromil sodium in this model is unknown.

2019 ◽  
Vol 20 (2) ◽  
pp. 146-156 ◽  
Author(s):  
Boris Ferko ◽  
Julia Romanova ◽  
Anastasia V. Rydlovskaya ◽  
Tatyana A. Kromova ◽  
Oxana V. Proskurina ◽  
...  

Background: Corticosteroids are the preferred option to treat asthma, however, they possess serious side effects and are inefficient in 10% of patients. Thus, new therapeutic approaches for asthma treatment are required. Objective: To study the efficacy of a novel glutarimide derivative XC8 in a Sephadex-induced lung inflammation in rats as well as in acute and chronic ovalbumin-induced allergic asthma in guinea pigs. Method: Rats were treated with 0.18-18 mg/kg of XC8 intragastrically 4 times (24 h and 1 h prior to and 24 h and 45 h after endotracheal administration of Sephadex). The number of inflammatory cells in bronchoalveaolar lavages (BAL) was determined. Guinea pigs were treated with 0.045 -1.4 mg/kg (acute asthma) or with 1.4 and 7.0 mg/kg of XC8 (chronic asthma) intragastrically following the sensitization with ovalbumin and during aerosol challenge. Lung inflammation, numbers of eosinophils (BAL and lung tissue), goblet cells, degranulating mast cells and specific airway resistance (sRAW) were determined. The comparator steroid drug budesonide (0.5 mg/kg for rats and 0.16 mg/kg for guinea pigs) was administered by inhalation. Results: XC8 reduced influx of eosinophils into BAL in Sephadex-induced lung inflammation model in rats (by 2.6-6.4 times). Treatment of acute asthma in guinea pigs significantly reduced eosinophils in guinea pigs in BAL (from 55% to 30%-39% of the total cell count) and goblet cells in lung tissue. In a model of acute and chronic asthma, XC8 reduced significantly the number of eosinophils and degranulating mast cells in the lung tissue. Treatment with XC8 but not with budesonide decreased the specific airway resistance in acute and chronic asthma model up to the level of naive animals. Conclusion: XC8 induced a profound anti-inflammatory effect by reducing eosinophils in BAL and eosinophils and degranulating mast cell numbers in the airway tissue. The anti-asthmatic effect of XC8 is comparable to that of budesonide. Moreover, in contrast to budesonide, XC8 was capable to reduce goblet cells and airway resistance.


Author(s):  
D.S. Friend ◽  
N. Ghildyal ◽  
M.F. Gurish ◽  
K.F. Austen ◽  
R.L. Stevens

Trichinella spiralis induces a profound mastocytosis and eosinophilia in the small intestine of the infected mouse. Mouse mast cells (MC) store in their granules various combinations of at least five chymotryptic chymases [designated mouse MC protease (mMCP) 1 to 5], two tryptic proteases designated mMCP-6 and mMCP-7 and an exopeptidase, carboxypeptidase A (mMC-CPA). Using antipeptide, protease -specific antibodies to these MC granule proteases, immunohistochemistry was done to determine the distribution, number and protease phenotype of the MCs in the small intestine and spleen 10 to >60 days after Trichinella infection of BALB/c and C3H mice. TEM was performed to evaluate the granule morphology of the MCs between intestinal epithelial cells and in the lamina propria (mucosal MCs) and in the submucosa, muscle and serosa of the intestine (submucosal MCs).As noted in the table below, the number of submucosal MCs remained constant throughout the study. In contrast, on day 14, the number of MCs in the mucosa increased ~25 fold. Increased numbers of MCs were observed between epithelial cells in the mucosal crypts, in the lamina propria and to a lesser extent, between epithelial cells of the intestinal villi.


2016 ◽  
Vol 48 (6) ◽  
pp. 1593-1601 ◽  
Author(s):  
Prathap Pillai ◽  
Yih-Chih Chan ◽  
Shih-Ying Wu ◽  
Line Ohm-Laursen ◽  
Clare Thomas ◽  
...  

Omalizumab therapy of non-atopic asthmatics reduces bronchial mucosal IgE and inflammation and preserves/improves lung function when disease is destabilised by staged withdrawal of therapy.18 symptomatic, non-atopic asthmatics were randomised (1:1) to receive omalizumab or identical placebo treatment in addition to existing therapy for 20 weeks. Bronchial biopsies were collected before and after 12–14 weeks of treatment, then the patients destabilised by substantial, supervised reduction of their regular therapy. Primary outcome measures were changes in bronchial mucosal IgE+ cells at 12–14 weeks, prior to regular therapy reduction, and changes in lung function (forced expiratory volume in 1 s) after destabilisation at 20 weeks. Quality of life was also monitored.Omalizumab but not placebo therapy significantly reduced median total bronchial mucosal IgE+ cells (p<0.01) but did not significantly alter median total mast cells, plasma cells, B lymphocytes, eosinophils and plasmablasts, although the latter were difficult to enumerate, being distributed as disperse clusters. By 20 weeks, lung function declined in the placebo-treated patients but improved in the omalizumab treated patients, with significant differences in absolute (p=0.04) and % predicted forced expiratory volume in 1 s (p=0.015).Omalizumab therapy of non-atopic asthmatics reduces bronchial mucosal IgE+ mast cells and improves lung function despite withdrawal of conventional therapy.


2010 ◽  
Vol 58 (3) ◽  
pp. 182 ◽  
Author(s):  
Swati Mittal ◽  
Usha Kumari ◽  
Pinky Tripathi ◽  
Ajay Kumar Mittal

The surface architecture of the epidermis on the outer surface of the operculum (OE) and the epithelium on the inner surface of the operculum (EISO) of Garra lamta was examined by scanning electron microscopy. The surface appeared smooth on the OE and wavy on the EISO. A wavy epithelium is considered to facilitate an increase in its stretchability, during the expansion of the branchial chamber. The OE and the EISO were covered by a mosaic pavement of epithelial cells with characteristic patterns of microridges and microbridges. Interspersed between the epithelial cells were mucous goblet cell pores, which were not significantly different in number in the OE and the EISO. Nevertheless, their surface area in the EISO was significantly higher than in the OE. This could be an adaptation to secrete higher amounts of mucus on the EISO for keeping the branchial chamber lining clean, avoiding clogging, the increased slipperiness reducing friction from water flow and increased efficiency in protecting against microbial attachments. Rounded bulges on the OE and the EISO were associated with mucous goblet cells. The absence of the taste buds in the EISO, in contrast to the OE, suggests that their function in the branchial chamber may not be of much significance in this fish. Breeding tubercles on the OE are believed to facilitate better contact between the male and female during breeding.


2013 ◽  
Vol 19 (9) ◽  
pp. 2342-2354 ◽  
Author(s):  
Mohammad W. Khan ◽  
Ali Keshavarzian ◽  
Elias Gounaris ◽  
Joshua E. Melson ◽  
Eric C. Cheon ◽  
...  

1947 ◽  
Vol s3-88 (3) ◽  
pp. 345-352
Author(s):  
E. MEIROWSKY ◽  
G. BEHR ◽  
S. KEYS

1. Goblet cells have been produced experimentally in rabbits' and guineapigs' corneae by ten methods. 2. Goblet cells can develop from ordinary epithelial cells. 3. The secretion antecedents originate in the nucleus. 4. Intranuclear and cytoplasmic inclusions can be produced experimentally and form the response mechanism of the cell towards animate and inanimate stimuli.


2018 ◽  
Vol 2018 ◽  
pp. 1-11
Author(s):  
Marcella Nebbioso ◽  
Marta Sacchetti ◽  
Guia Bianchi ◽  
Anna Maria Zicari ◽  
Marzia Duse ◽  
...  

Background. Vernal keratoconjunctivitis (VKC) is a rare ocular surface inflammatory disease that affects mainly boys in the first decade of life. Clinical observations show that it generally regresses spontaneously with the onset of puberty, but therapeutic measures must be taken before then to control the course of the disease. Purpose.To evaluate the role of the lacrimal mucous component in VKC patients and compare tear ferning test (TFT) modifications, MUC5AC levels in tears, and density of conjunctival goblet cells to clinical characteristics before and after treatment with cyclosporine A (CY) in eye drops. Methods. Forty-seven patients affected by VKC and 30 healthy subjects aged between 3 and 16 years of life were enrolled. All individuals were submitted to complete eye examination and skin prick test (SPT) for the most common allergens. Then, they were subjected to collection of the tears and to impression cytology to evaluate TFT, MUC5AC levels, and conjunctival goblet cell density, before and after treatment with CY in eye drops. Results. Comparing the VKC group vs. the control group at baseline, a significant alteration in the degree of the ferns was found, indicating a pathological condition of the lacrimal mucous layer. In addition, an increased number of goblet cells were observed in the patients. The concentration of lacrimal secretory mucins (MUC5AC) did not show significant differences between the 2 groups. Patients treated with CY have reported improvements of some signs and symptoms of disease activity, including TFT, and a tendency of conjunctival goblet cell density to normalise. Conclusions. The results obtained demonstrated for the first time a significant alteration of the lacrimal mucin component evaluated in the VKC group, and an improvement of the latter after CY therapy.


2008 ◽  
Vol 8 (3) ◽  
pp. 453-457 ◽  
Author(s):  
Mali Wirotesangthong ◽  
Naoki Inagaki ◽  
Hiroyuki Tanaka ◽  
Witchuda Thanakijcharoenpath ◽  
Hiroichi Nagai

2001 ◽  
Vol 280 (2) ◽  
pp. L316-L325 ◽  
Author(s):  
Kazuyoshi Kuwano ◽  
Ritsuko Kunitake ◽  
Takashige Maeyama ◽  
Naoki Hagimoto ◽  
Masayuki Kawasaki ◽  
...  

Caspases have been implicated in the effector process of apoptosis in several systems including the Fas-Fas ligand pathway. We previously demonstrated that excessive apoptosis of lung epithelial cells and the Fas-Fas ligand pathway were essential in the pathogenesis of bleomycin-induced pneumopathy in mice. Therefore, the purpose of this study was to investigate whether a caspase inhibitor could prevent the development of this model. The expression of caspase-1 and caspase-3 was upregulated on lung epithelial cells, alveolar macrophages, and infiltrating inflammatory cells in this model. We demonstrated that a broad-spectrum caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, decreased the caspase-1- and caspase-3-like activity, the number of apoptotic cells, the pathological grade of lung inflammation and fibrosis, and the hydroxyproline content in lung tissues in this model. We conclude that caspase inhibitors could be a new therapeutic approach against lung injury and pulmonary fibrosis.


Rheumatology ◽  
2018 ◽  
Vol 58 (4) ◽  
pp. 617-627 ◽  
Author(s):  
Sijia Chen ◽  
Troy Noordenbos ◽  
Iris Blijdorp ◽  
Leonieke van Mens ◽  
Carmen A Ambarus ◽  
...  

Abstract Objectives Synovial mast cells contain IL-17A, a key driver of tissue inflammation in SpA. A recent in vitro study showed that tissue-derived mast cells can capture and release exogenous IL-17A. The present study aimed to investigate if this mechanism could contribute to tissue inflammation in SpA. Methods Potential activation of mast cells by IL-17A was assessed by gene expression analysis of the Laboratory of Allergic Diseases 2 (LAD2) mast cell line. The presence of IL-17A-positive mast cells was assessed by immunohistochemistry in synovial tissue obtained before and after secukinumab treatment, as well as in skin and gut tissues from SpA-related conditions. Results IL-17A did not induce a pro-inflammatory response in human LAD2 mast cells according to the canonical IL-17A signalling pathway. In SpA synovial tissue, the percentage of IL-17A-positive mast cells increased upon treatment with secukinumab. IL-17A-positive mast cells were also readily detectable in non-inflamed barrier tissues such as skin and gut. In non-inflamed dermis and gut submucosa, IL-17A-positive mast cells are the most prevalent IL-17A-positive cells in situ. Compared with non-inflamed tissues, both total mast cells and IL-17A-positive mast cells were increased in psoriatic skin dermis and in submucosa from inflammatory bowel disease gut. In contrast, the proportion of IL-17A-positive mast cells was strikingly lower in the inflamed compared with non-inflamed gut lamina propria. Conclusion IL-17A-positive mast cells are present across SpA target tissues and correlate inversely with inflammation, indicating that their IL-17A content can be regulated. Tissue-resident mast cells may act as IL-17A-loaded sentinel cells, which release IL-17A to amplify tissue inflammation.


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