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Adoptively transferred late allergic response is inhibited by IL-4, but not IL-5, antisense oligonucleotide.

https://arctichealth.org/en/permalink/ahliterature15653
Source
J Allergy Clin Immunol. 1999 Jul;104(1):205-14
Publication Type
Article
Date
Jul-1999
Author
S. Molet
D. Ramos-Barbón
J G Martin
Q. Hamid
Author Affiliation
Meakins-Christie Laboratories, McGill University, Montréal, Quebec, Canada.
Source
J Allergy Clin Immunol. 1999 Jul;104(1):205-14
Date
Jul-1999
Language
English
Publication Type
Article
Keywords
Adoptive Transfer
Animals
Asthma - immunology - prevention & control
Bronchoalveolar Lavage Fluid - chemistry - cytology
CD4-Positive T-Lymphocytes - drug effects
Cell Survival
Cells, Cultured
Cytokines - immunology
Disease Models, Animal
Immunohistochemistry
Interleukin-4 - immunology - therapeutic use
Interleukin-5 - immunology - therapeutic use
Male
Oligonucleotides, Antisense - therapeutic use
Ovalbumin - pharmacology
Pulmonary Eosinophilia - metabolism
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Th2 Cells - immunology
Abstract
BACKGROUND: We have shown previously that the late airways response (LAR) can be transferred by ovalbumin-primed CD4(+) T lymphocytes in Brown Norway rats. This response is associated with an increase of eosinophils and high expression of TH2 cytokines (IL-4 and IL-5) in bronchoalveolar lavage (BAL) fluid. OBJECTIVE: In this study we hypothesized that the inhibition of IL-4 or IL-5 production in the CD4(+) cells transferred to a naive animal could decrease the LAR and prevent airway eosinophilia in response to antigen challenge. METHODS: CD4(+) cells, purified from the cervical lymph nodes of ovalbumin-sensitized rats, were maintained in culture for 6 hours with medium alone or with 10 microgram/mL IL-4 antisense (AS), IL-5 AS, or control AS oligodeoxynucleotide. Then the cells were administrated intraperitoneally to naive rats, which were challenged 2 days later by a 5% ovalbumin aerosol. The lung resistance was measured for 8 hours, and then BAL was performed. Cytospin preparations from BAL cells were assessed for the presence of eosinophils by immunocytochemistry for major basic protein and for IL-4, IL-5, and IFN-gamma expression. RESULTS: In rats injected with IL-4 AS-treated T cells, LAR, eosinophils, and IL-4 and IL-5 expression were significantly decreased compared with the other groups. Only IL-5 expression in BAL fluid was slightly decreased consequent to the transfer of IL-5 AS-treated T cells. CONCLUSION: This study demonstrates that, in the CD4(+) T cell-driven LAR, the early production of IL-4, but not IL-5, by the transferred CD4(+) cells is essential for the development of the LAR.
Notes
Erratum In: J Allergy Clin Immunol 1999 Dec;104(6):1188
PubMed ID
10400863 View in PubMed
Less detail

Altered microRNA profiles in bronchoalveolar lavage fluid exosomes in asthmatic patients.

https://arctichealth.org/en/permalink/ahliterature117113
Source
J Allergy Clin Immunol. 2013 Mar;131(3):894-903
Publication Type
Article
Date
Mar-2013
Author
Bettina Levänen
Nirav R Bhakta
Patricia Torregrosa Paredes
Rebecca Barbeau
Stefanie Hiltbrunner
Joshua L Pollack
C Magnus Sköld
Magnus Svartengren
Johan Grunewald
Susanne Gabrielsson
Anders Eklund
Britt-Marie Larsson
Prescott G Woodruff
David J Erle
Åsa M Wheelock
Author Affiliation
Respiratory Medicine Unit, Department of Medicine, and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. bettina.levanen@ki.se
Source
J Allergy Clin Immunol. 2013 Mar;131(3):894-903
Date
Mar-2013
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Air Pollutants - toxicity
Asthma - genetics - physiopathology
Bronchoalveolar Lavage Fluid - chemistry
Case-Control Studies
Cytokines - genetics
Environmental Exposure
Exosomes - genetics
Female
Forced expiratory volume
Humans
Janus Kinases - genetics
Male
MicroRNAs - analysis
Mitogen-Activated Protein Kinases - genetics
STAT Transcription Factors - genetics
Sweden
Vital Capacity
Young Adult
Abstract
Asthma is characterized by increased airway narrowing in response to nonspecific stimuli. The disorder is influenced by both environmental and genetic factors. Exosomes are nanosized vesicles of endosomal origin released from inflammatory and epithelial cells that have been implicated in asthma. In this study we characterized the microRNA (miRNA) content of exosomes in healthy control subjects and patients with mild intermittent asthma both at unprovoked baseline and in response to environmental challenge.
To investigate alterations in bronchoalveolar lavage fluid (BALF) exosomal miRNA profiles due to asthma, and following subway air exposure.
Exosomes were isolated from BALF from healthy control subjects (n = 10) and patients with mild intermittent asthma (n = 10) after subway and control exposures. Exosomal RNA was analyzed by using microarrays containing probes for 894 human miRNAs, and selected findings were validated with quantitative RT-PCR. Results were analyzed by using multivariate modeling.
The presence of miRNAs was confirmed in exosomes from BALF of both asthmatic patients and healthy control subjects. Significant differences in BALF exosomal miRNA was detected for 24 miRNAs with a subset of 16 miRNAs, including members of the let-7 and miRNA-200 families, providing robust classification of patients with mild nonsymptomatic asthma from healthy subjects with 72% cross-validated predictive power (Q(2) = 0.72). In contrast, subway exposure did not cause any significant alterations in miRNA profiles.
These studies demonstrate substantial differences in exosomal miRNA profiles between healthy subjects and patients with unprovoked, mild, stable asthma. These changes might be important in the inflammatory response leading to bronchial hyperresponsiveness and asthma.
Notes
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Comment In: J Allergy Clin Immunol. 2013 Mar;131(3):904-523360758
PubMed ID
23333113 View in PubMed
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Asbestos bodies in bronchoalveolar lavage fluid in relation to occupational history.

https://arctichealth.org/en/permalink/ahliterature217050
Source
Am J Ind Med. 1994 Nov;26(5):645-54
Publication Type
Article
Date
Nov-1994
Author
A. Karjalainen
S. Anttila
T. Mäntylä
E. Taskinen
P. Kyyrönen
P. Tukiainen
Author Affiliation
Institute of Occupational Health, Helsinki, Finland.
Source
Am J Ind Med. 1994 Nov;26(5):645-54
Date
Nov-1994
Language
English
Publication Type
Article
Keywords
Adult
Aged
Aged, 80 and over
Analysis of Variance
Asbestos - analysis
Asbestosis - epidemiology
Bronchoalveolar Lavage Fluid - chemistry
Female
Finland - epidemiology
Humans
Interviews as Topic
Male
Middle Aged
Occupational Exposure - analysis - statistics & numerical data
Smoking - epidemiology
Abstract
Concentrations of asbestos bodies (AB) were assessed by optical microscopy of 10 ml iron-stained samples and compared with the exposure history acquired by personal interview for 156 patients. Concentrations equalling or exceeding 1 AB/ml were found in 85% of patients who had been heavily exposed to asbestos and only 7% of those who were unlikely to have been exposed. Elevated AB concentrations were observed among primary asbestos, shipyard and construction workers. Smoking was not found to affect the AB concentrations. The use of Papanicolaou-stained cytological Millipore preparations during routine screening was a less sensitive method for the assessment of AB concentrations than that involving iron-stained preparations. The expression of AB concentration as AB/ml or AB/million cells were found to be equally useful indicators of exposure. The correlation between AB concentration and exposure history was greater than in earlier studies on workers exposed to chrysotile. Concentrations exceeding 1 AB/ml were indicative of a nontrivial exposure to asbestos. Despite the observed correlation between AB concentration and exposure history, the individual variability of AB counts, methodological differences and laboratory-bound reference values are important in the interpretation of AB concentrations in bronchoalveolar lavage (BAL) fluid at individual level.
PubMed ID
7832212 View in PubMed
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Asbestos bodies in bronchoalveolar lavage in relation to asbestos bodies and asbestos fibres in lung parenchyma.

https://arctichealth.org/en/permalink/ahliterature211977
Source
Eur Respir J. 1996 May;9(5):1000-5
Publication Type
Article
Date
May-1996
Author
A. Karjalainen
R. Piipari
T. Mäntylä
M. Mönkkönen
M. Nurminen
P. Tukiainen
E. Vanhala
S. Anttila
Author Affiliation
Finnish Institute of Occupational Health, Helsinki, Finland.
Source
Eur Respir J. 1996 May;9(5):1000-5
Date
May-1996
Language
English
Publication Type
Article
Keywords
Adult
Aged
Aged, 80 and over
Asbestos - adverse effects - analysis
Bronchoalveolar Lavage Fluid - chemistry
Culture Techniques
Finland
Humans
Lung - chemistry
Microscopy, Electron
Middle Aged
Mineral Fibers - adverse effects - analysis
Abstract
In Finland, unlike other countries, anthophyllite asbestos has been widely used due to its domestic production in 1918-1975. In this particular context, the aim of the present study was to analyse the relationship between asbestos bodies (ABs) in bronchoalveolar lavage (BAL) fluid and the concentration of ABs and the different amphibole asbestos fibres in lung tissue. Sixty five BAL lung tissue sample pairs from patients with pulmonary disease were analysed. The concentration of ABs in BAL fluid and lung tissue was determined with optical microscopy, and the concentration, type and dimensions of asbestos fibres in lung tissue with scanning electron microscopy. There was a significant correlation between the concentrations of ABs in BAL fluid and in lung tissue (r = 0.72; p
PubMed ID
8793463 View in PubMed
Less detail

Bile acid aspiration and the development of bronchiolitis obliterans after lung transplantation.

https://arctichealth.org/en/permalink/ahliterature174993
Source
J Thorac Cardiovasc Surg. 2005 May;129(5):1144-52
Publication Type
Article
Date
May-2005
Author
Frank D'Ovidio
Marco Mura
Melanie Tsang
Thomas K Waddell
Michael A Hutcheon
Lianne G Singer
Denis Hadjiliadis
Cecilia Chaparro
Carlos Gutierrez
Andrew Pierre
Gail Darling
Mingyao Liu
Shaf Keshavjee
Author Affiliation
Toronto Lung Transplant Program, University of Toronto, Toronto General Hospital, 200 Elizabeth Street, Toronto, Ontario, Canada M5G 2C4.
Source
J Thorac Cardiovasc Surg. 2005 May;129(5):1144-52
Date
May-2005
Language
English
Publication Type
Article
Keywords
Actuarial Analysis
Bile Acids and Salts - adverse effects - analysis
Biological Markers - analysis
Bronchiolitis Obliterans - diagnosis - epidemiology - etiology
Bronchoalveolar Lavage Fluid - chemistry - cytology
Bronchoscopy
Disease-Free Survival
Enzyme-Linked Immunosorbent Assay
Follow-Up Studies
Gastroesophageal Reflux - complications
Humans
Inflammation
Interleukin-15 - analysis - immunology
Interleukin-8 - analysis - immunology
Leukocyte Count
Lung Transplantation - adverse effects
Neutrophils - immunology
Ontario - epidemiology
Prevalence
Respiratory Function Tests
Risk factors
Spectrophotometry
Survival Analysis
Time Factors
Abstract
Aspiration of gastroesophageal refluxate may contribute to lung transplant bronchiolitis obliterans syndrome (BOS). We investigated bile acids in bronchoalveolar lavage fluid (BALF) and studied its role in BOS.
Surveillance pulmonary function tests and BALF were evaluated in 120 lung recipients. BOS-(0p-3) was diagnosed after 6 months' survival. BOS was defined as "early" if diagnosed within 12 months after a transplant. BALF was assayed for differential cell count, bile acids, and interleukins 8 and 15. Bile acids were considered elevated if greater than normal serum levels ( or =8 micromol/L).
Elevated BALF bile acids were measured in 20 (17%) of 120 patients. BOS was diagnosed in 36 (34%) of 107 patients and judged "early" in 21 (57%) of 36. Median BALF bile acid values were 1.6 micromol/L (range, 0-32 micromol/L) in BOS patients and 0.3 micromol/L (range, 0-16 micromol/L) in non-BOS patients ( P = .002); 2.6 micromol/L (range, 0-32 micromol/L) in early BOS patients and 0.8 micromol/L (range, 0-4.6 micromol/L) in late BOS patients, ( P = .02). Bile acids correlated with BALF IL-8 and alveolar neutrophilia (r = 0.3, P = .0004, and r = 0.3, P = .004, respectively), but not with IL-15. Freedom from BOS was significantly shortened in patients with elevated BALF bile acids (Cox-Mantel test, P = .0001).
Aspiration of duodenogastroesophageal refluxate is prevalent after lung transplantation and is associated with the development of BOS. Elevated BALF bile acids may promote early BOS development via an inflammatory process, possibly mediated by IL-8 and alveolar neutrophilia.
PubMed ID
15867792 View in PubMed
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Capsaicin-induced mucus secretion in rat airways assessed in vivo and non-invasively by magnetic resonance imaging.

https://arctichealth.org/en/permalink/ahliterature78515
Source
Br J Pharmacol. 2007 Apr;150(8):1022-30
Publication Type
Article
Date
Apr-2007
Author
Karmouty-Quintana H.
Cannet C.
Sugar R.
Fozard J R
Page C P
Beckmann N.
Author Affiliation
Discovery Technologies, Novartis Institutes for BioMedical Research, Basel, Switzerland.
Source
Br J Pharmacol. 2007 Apr;150(8):1022-30
Date
Apr-2007
Language
English
Publication Type
Article
Keywords
Animals
Aza Compounds - pharmacology
Benzamides - pharmacology
Bronchoalveolar Lavage Fluid - chemistry - cytology
Capsaicin - analogs & derivatives - pharmacology
Cromolyn Sodium - pharmacology
Goblet Cells - drug effects - metabolism - pathology
Lung - drug effects - innervation - metabolism - pathology
Magnetic Resonance Imaging
Male
Mucus - secretion
Neurons, Afferent - drug effects
Rats
Rats, Inbred BN
Receptors, Neurokinin-1 - drug effects - metabolism
Receptors, Neurokinin-2 - drug effects - metabolism
TRPV Cation Channels - drug effects - metabolism
Time Factors
Abstract
BACKGROUND AND PURPOSE: An up-regulation of the sensory neural pathways in the lung has been implicated in asthma and chronic obstructive pulmonary disease (COPD) and is thought to contribute to mucus hypersecretion, an essential feature of both diseases. The aim of this study was to assess non-invasively the acute effects (up to 60 min) of sensory nerve stimulation by capsaicin in the lung, using magnetic resonance imaging (MRI). EXPERIMENTAL APPROACH: Male Brown Norway rats were imaged prior to and 10, 30 and 60 min after intra-tracheal challenge with capsaicin (30 microg kg(-1)) or vehicle (0.5% ethanol solution). In subsequent studies, pre-treatment with the transient receptor potential vanilloid (TRPV)-1 antagonist, capsazepine; the dual neurokinin (NK) 1 and NK2 receptor antagonist, DNK333 and the mast cell stabilizer, di-sodium cromoglycate (DSCG) was used to modulate the effects of capsaicin. KEY RESULTS: Diffuse fluid signals were detected by MRI in the lung as early as 10 min after capsaicin, remaining constant 30 and 60 min after treatment. Broncho-alveolar lavage (BAL) fluid analysis performed 60 min after capsaicin revealed increased mucin concentration. Capsazepine (3.5 mg kg(-1)), DNK333 (10 mg kg(-1)) but not DSCG (10 mg kg(-1)) administered prophylactically were able to block the effect of capsaicin in the airways. CONCLUSIONS AND IMPLICATIONS: These observations suggest that the fluid signals detected by MRI after capsaicin administration reflected predominantly the release of mucus following activation of sensory nerves. They point to the opportunity of non-invasively assessing with MRI the influence of neuronal mechanisms in animal models of asthma and COPD.
PubMed ID
17351665 View in PubMed
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CD4+ T cells can induce airway hyperresponsiveness to allergen challenge in the brown norway rat.

https://arctichealth.org/en/permalink/ahliterature57554
Source
Am J Respir Crit Care Med. 1998 Dec;158(6):1863-70
Publication Type
Article
Date
Dec-1998
Author
H. Mishima
M. Hojo
A. Watanabe
Q A Hamid
J G Martin
Author Affiliation
Meakins-Christie Laboratories, Royal Victoria Hospital, McGill University, and the Respiratory Health Network of Centres of Excellence, Montreal, Quebec, Canada.
Source
Am J Respir Crit Care Med. 1998 Dec;158(6):1863-70
Date
Dec-1998
Language
English
Publication Type
Article
Keywords
Aerosols
Allergens - immunology
Animals
Bronchial Hyperreactivity - immunology
Bronchial Provocation Tests
Bronchoalveolar Lavage Fluid - chemistry - immunology
Bronchoconstrictor Agents - diagnostic use
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - immunology
Cattle
Comparative Study
Eosinophilia - immunology
Gene Expression Regulation
Immunization
Immunoglobulin E - immunology
In Situ Hybridization
Interferon Type II - genetics - immunology
Interleukin-5 - genetics - immunology
Male
Methacholine Chloride - diagnostic use
Ovalbumin - immunology
Proteins - analysis
RNA, Messenger - genetics
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Serum Albumin, Bovine - immunology
Time Factors
Abstract
Airway hyperresponsiveness to inhalational challenge with methacholine (MCh) develops by 32 h after allergen challenge of actively sensitized BN rats. To test the hypothesis that CD4+ T cells mediate allergen-induced hyperresponsiveness independent of IgE-mediated mechanisms, we administered CD4+ T cells, CD8+ T cells, and a mixture of CD4+ and CD8+ T cells (total T cells) isolated from the cervical lymph nodes of rats sensitized with ovalbumin (OA) to naive BN rats that underwent aerosol challenge with either OA or bovine serum albumin (BSA) 2 d later. Responsiveness to MCh was measured 2 d before transfer of T cells and 32 h after challenge with OA or BSA. Airway responsiveness increased significantly in recipients of CD4+ T cells after OA challenge, but not in any other of the treatment groups. Analysis of bronchoalveolar lavage (BAL) cells for major basic protein expression by immunostaining showed eosinophilia in OA-challenged CD4+ and total T-cell recipients. Cells retrieved by bronchoalveolar lavage showed increased expression of IL-5 mRNA (in situ hybridization) in CD4+ T cell recipients after OA challenge compared with other groups. Interferon-gamma mRNA was expressed to the greatest extent in CD8+ recipients, but it was elevated in both OA- and BSA-challenged animals. We conclude that CD4+ T cells can induce airway hyperresponsiveness after inhalational challenge with allergen and this is associated with IL-5 production and eosinophilia. CD8+ T cells may have a negative regulatory effect on responsiveness, possibly mediated by interferon-gamma.
PubMed ID
9847279 View in PubMed
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Chronic postbronchiolitis airway instability induced with anti-IFN-gamma antibody in F344 rats.

https://arctichealth.org/en/permalink/ahliterature15345
Source
Pediatr Res. 2002 Sep;52(3):382-6
Publication Type
Article
Date
Sep-2002
Author
Ronald L Sorkness
William L Castleman
Lance D Mikus
Anne G Mosser
Robert F Lemanske
Author Affiliation
Division of Allergy and Immunology, Department of Medicine, University of Wisconsin, Madison, Wisconsin 53792, USA. RLSORKNE@facstaff.wisc.edu
Source
Pediatr Res. 2002 Sep;52(3):382-6
Date
Sep-2002
Language
English
Publication Type
Article
Keywords
Airway Resistance - physiology
Animals
Antibodies - immunology
Asthma - physiopathology
Bronchiolitis - physiopathology
Bronchoalveolar Lavage Fluid - chemistry
Chronic Disease
Humans
Interferon Type II - immunology - metabolism
Male
Rats
Rats, Inbred F344
Research Support, U.S. Gov't, P.H.S.
Time Factors
Abstract
Analogous to childhood-onset asthma in humans, rats may develop a chronic asthmalike phenotype, depending on their genetic background and the age at which they experience a viral airway injury. Brown Norway rats develop a postbronchiolitis asthmalike phenotype that may be prevented with supplements of interferon-gamma (IFN-gamma); we hypothesized that the normally resistant F344 rat strain would develop the asthmalike phenotype if the IFN-gamma response were suppressed during viral illness. Weanling F344 rats were pretreated with anti-IFN-gamma or control antibody, and inoculated with Sendai virus or vehicle. Anti-IFN-gamma treatment reduced lung IFN-gamma and increased IL-4 mRNA during the infection. Physiologic studies performed 8 wk later revealed premature airway closure (p = 0.03) and elevated specific pulmonary resistance (p
PubMed ID
12193672 View in PubMed
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Clinical utility and prognostic value of bronchoalveolar lavage galactomannan in patients with hematologic malignancies.

https://arctichealth.org/en/permalink/ahliterature140758
Source
Diagn Microbiol Infect Dis. 2010 Oct;68(2):132-9
Publication Type
Article
Date
Oct-2010
Author
Me-Linh Luong
Charles Filion
Annie-Claude Labbé
Jean Roy
Jacques Pépin
Julia Cadrin-Tourigny
Stéphane Carignan
Donald C Sheppard
Michel Laverdière
Author Affiliation
Department of Microbiology, McGill University Health Center, Montreal, Quebec, Canada.
Source
Diagn Microbiol Infect Dis. 2010 Oct;68(2):132-9
Date
Oct-2010
Language
English
Publication Type
Article
Keywords
Antigens, Fungal - analysis
Aspergillus - immunology - isolation & purification
Bronchoalveolar Lavage
Bronchoalveolar Lavage Fluid - chemistry
Bronchoscopy
Canada
Cohort Studies
Female
Hematologic Neoplasms - complications
Hematopoietic Stem Cell Transplantation
Humans
Immunoenzyme Techniques
Invasive Pulmonary Aspergillosis - diagnosis - microbiology
Male
Mannans - analysis - immunology
Middle Aged
Mycological Typing Techniques
Opportunistic Infections - diagnosis - microbiology
Predictive value of tests
Prognosis
Retrospective Studies
Sensitivity and specificity
Abstract
We conducted a single-center retrospective cohort study to determine the performance characteristics of the galactomannan (GM) assay in bronchoalveolar lavage (BAL) in patients with hematologic malignancies. Patients were classified as proven, probable, possible, or no invasive pulmonary aspergillosis (IPA), according to international guidelines. A total of 173 BAL samples from 145 patients were included. There were 5 proven, 7 probable, and 35 possible cases of IPA. Using a GM index cutoff of = 0.5, the sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) of the BAL GM assay were 100%, 78%, 26%, and 100%, respectively. Using a GM index cutoff of = 2.0, the sensitivity and NPV remained 100%, but specificity and PPV increased to 93% and 50%, respectively. The BAL GM assay is a highly sensitive screening test for IPA in patients with hematologic malignancies. Increasing the cutoff value to 2.0 would improve the performance of this assay.
PubMed ID
20846585 View in PubMed
Less detail

Comparative microarray analysis and pulmonary changes in Brown Norway rats exposed to ovalbumin and concentrated air particulates.

https://arctichealth.org/en/permalink/ahliterature90256
Source
Toxicol Sci. 2009 Mar;108(1):207-21
Publication Type
Article
Date
Mar-2009
Author
Heidenfelder Brooke L
Reif David M
Harkema Jack R
Cohen Hubal Elaine A
Hudgens Edward E
Bramble Lori A
Wagner James G
Morishita Masako
Keeler Gerald J
Edwards Stephen W
Gallagher Jane E
Author Affiliation
Human Studies Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Source
Toxicol Sci. 2009 Mar;108(1):207-21
Date
Mar-2009
Language
English
Publication Type
Article
Keywords
Air Pollutants - toxicity
Allergens - administration & dosage - immunology
Analysis of Variance
Animals
Bronchoalveolar Lavage Fluid - chemistry - immunology
Bronchopneumonia - metabolism - pathology
Gene Expression - drug effects
Inflammation - immunology
Lung - drug effects - immunology - metabolism - pathology
Male
Oligonucleotide Array Sequence Analysis
Ovalbumin - administration & dosage - immunology
Particulate Matter - administration & dosage - toxicity
Principal Component Analysis
Rats
Respiratory Hypersensitivity - metabolism - pathology
Respiratory Mucosa - drug effects - immunology - metabolism - pathology
Abstract
The interaction between air particulates and genetic susceptibility has been implicated in the pathogenesis of asthma. The overall objective of this study was to determine the effects of inhalation exposure to environmentally relevant concentrated air particulates (CAPs) on the lungs of ovalbumin (ova) sensitized and challenged Brown Norway rats. Changes in gene expression were compared with lung tissue histopathology, morphometry, and biochemical and cellular parameters in bronchoalveolar lavage fluid (BALF). Ova challenge was responsible for the preponderance of gene expression changes, related largely to inflammation. CAPs exposure alone resulted in no significant gene expression changes, but CAPs and ova-exposed rodents exhibited an enhanced effect relative to ova alone with differentially expressed genes primarily related to inflammation and airway remodeling. Gene expression data was consistent with the biochemical and cellular analyses of the BALF, the pulmonary pathology, and morphometric changes when comparing the CAPs-ova group to the air-saline or CAPs-saline group. However, the gene expression data were more sensitive than the BALF cell type and number for assessing the effects of CAPs and ova versus the ova challenge alone. In addition, the gene expression results provided some additional insight into the TGF-beta-mediated molecular processes underlying these changes. The broad-based histopathology and functional genomic analyses demonstrate that exposure to CAPs exacerbates rodents with allergic inflammation induced by an allergen and suggests that asthmatics may be at increased risk for air pollution effects.
PubMed ID
19176365 View in PubMed
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