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Airway Remodeling in Allergen Challenged Brown Norway Rats: Distribution of Proteoglycans.

https://arctichealth.org/en/permalink/ahliterature14996
Source
Am J Physiol Lung Cell Mol Physiol. 2005 Dec 30;
Publication Type
Article
Date
Dec-30-2005
Author
Laura Pini
Chiara Torregiani
James G Martin
Qutayba Hamid
Mara S Ludwig
Author Affiliation
Department of Medicine, Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Source
Am J Physiol Lung Cell Mol Physiol. 2005 Dec 30;
Date
Dec-30-2005
Language
English
Publication Type
Article
Abstract
Proteoglycans (PG) have important effects on the mechanical properties of tissues, and the phenotype of various structural cells. Little is known about changes in PG deposition in the airways in animal models of asthma. We studied changes in PG in the airway wall of Brown Norway rats sensitized to ovalbumin (OA) and exposed to repeated OA challenge. Control (Sal) animals were sensitized and challenged with saline. After the 3rd challenge, animals were sacrificed and lungs fixed in formalin. Tissue sections were incubated with antibodies to the small, leucine-rich PG, decorin and biglycan, and collagen type I. Airways were classified according to basement membrane perimeter (Pbm) length (/=3mm). Decorin, biglycan and collagen type I, were increased in the airways of OA vs Sal rats. Remodeling was most prominent in central airways. The distribution of PG differed with respect to the subepithelial vs airway smooth muscle (ASM) vs adventitial layer. Whereas biglycan was readily detected within the ASM, decorin and collagen were detected outside the ASM, and especially in the adventitial layer. Differences in the distribution of these molecules within the layers of the airway wall may reflect their specific functional roles.
PubMed ID
16387756 View in PubMed
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CD8+ alphabeta T cells can mediate late airway responses and airway eosinophilia in rats.

https://arctichealth.org/en/permalink/ahliterature57391
Source
J Allergy Clin Immunol. 2004 Dec;114(6):1345-52
Publication Type
Article
Date
Dec-2004
Author
Susumu Isogai
Rame Taha
Meiyo Tamaoka
Yasuyuki Yoshizawa
Qutayba Hamid
James G Martin
Author Affiliation
Department of Medicine, McGill University, Montreal, Quebec, Canada.
Source
J Allergy Clin Immunol. 2004 Dec;114(6):1345-52
Date
Dec-2004
Language
English
Publication Type
Article
Keywords
Adoptive Transfer
Animals
Bronchoalveolar Lavage Fluid - immunology
CD8-Positive T-Lymphocytes - immunology
Cytokines - biosynthesis
Eosinophilia - etiology
Lung Diseases - etiology
Male
Ovalbumin - immunology
Rats
Rats, Inbred BN
Receptors, Antigen, T-Cell, alpha-beta - analysis
Research Support, Non-U.S. Gov't
Abstract
BACKGROUND: The function of CD8+ T-cell subsets in mediating late allergic responses is incompletely understood. OBJECTIVE: We sought to test the hypothesis that CD8+ alphabeta T cells are proinflammatory in the airways in vivo by using a well-characterized animal model and the technique of adoptive transfer. METHODS: Brown Norway rats were administered CD8 + alphabeta T cells (10 6 ) intraperitoneally purified from lymph node cells of either naive or ovalbumin (OVA)-sensitized rats and were challenged with aerosolized OVA 2 days later. Control rats were sensitized to 100 mug of OVA in Al(OH) 3 subcutaneously or sham sensitized to saline and were OVA challenged 2 weeks later. RESULTS: The OVA-sensitized and OVA-challenged group and the recipients of OVA-primed CD8+ alphabeta T cells had significant late airway responses calculated from lung resistance measured for an 8-hour period after challenge compared with the naive CD8 + alphabeta T cell-transferred group and the sham-sensitized control group. The number of eosinophils in bronchoalveolar lavage fluid increased in the OVA-sensitized group and the OVA-primed CD8+ alphabeta T-cell recipients compared with numbers in the naive CD8+ alphabeta T-cell recipients and the sham-sensitized control group. IL-4 and IL-5 cytokine mRNA expression in bronchoalveolar lavage fluid increased in the OVA-sensitized group and the OVA-primed CD8+ alphabeta T-cell recipients compared with that in the sham-sensitized group. CONCLUSION: We conclude that antigen-primed CD8 + alphabeta T cells might have a proinflammatory role in allergen-driven airway responses in the rat.
PubMed ID
15577833 View in PubMed
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The effects of CD8+gammadelta T cells on late allergic airway responses and airway inflammation in rats.

https://arctichealth.org/en/permalink/ahliterature57418
Source
J Allergy Clin Immunol. 2003 Sep;112(3):547-55
Publication Type
Article
Date
Sep-2003
Author
Susumu Isogai
Alexandra Rubin
Karim Maghni
David Ramos-Barbon
Rame Taha
Yasuyuki Yoshizawa
Qutayba Hamid
James G Martin
Author Affiliation
Meakins Christie Laboratories, Department of Medicine, McGill University, 3623 St Urbain, Montreal, Quebec, Canada H2X 2P2.
Source
J Allergy Clin Immunol. 2003 Sep;112(3):547-55
Date
Sep-2003
Language
English
Publication Type
Article
Keywords
Adoptive Transfer
Allergens - administration & dosage
Animals
CD8-Positive T-Lymphocytes - immunology
Cytokines - biosynthesis - genetics
Eosinophilia - immunology
Immunoglobulin E - blood
Interferon Type II - biosynthesis - genetics
Interleukin-4 - biosynthesis - genetics
Male
Models, Immunological
Ovalbumin - administration & dosage - immunology
RNA, Messenger - genetics - metabolism
Rats
Rats, Inbred BN
Receptors, Antigen, T-Cell, gamma-delta - metabolism
Research Support, Non-U.S. Gov't
Respiratory Hypersensitivity - etiology - immunology
T-Lymphocyte Subsets - immunology
Abstract
BACKGROUND: Gamma-delta (gammadelta) T cells regulate immune responses to foreign protein at mucosal surfaces. Whether they can modify allergen-induced early (EAR) and late airway responses (LAR) is unknown. OBJECTIVE: We have tested the hypothesis that the CD8+ subtype of gammadelta T cells decreases allergen-induced LAR and airway eosinophilia in the rat. METHODS: Brown Norway rats were administered, intraperitoneally, 3.5 x 10(4) lymph node CD8+gammadelta T cells from naive or sensitized rats. The recipients were sensitized to ovalbumin (OVA) in Al(OH)(3) 3 days after cell transfer and challenged with aerosolized OVA 14 days later. Serum IgE was measured before allergen challenge. After challenge, lung resistance was monitored for 8 hours and then bronchoalveolar lavage (BAL) was analyzed for eosinophil major basic protein (MBP), IL-4, IL-5, IL-13, and IFN-gamma messenger RNA-expressing cells. RESULTS: gammadelta T cells from naive donors significantly decreased LAR in OVA-challenged sensitized rats, whereas MBP(+) eosinophils were decreased by both gammadelta T cells from naive and sensitized donors. EAR and serum IgE levels were unchanged. The expression of IL-4, IL-5, and IL-13 by BAL cells of gammadelta T cell recipients was attenuated compared with OVA-challenged controls. This was accompanied by an increase in the expression of IFN-gamma. CONCLUSIONS: Our results are consistent with a suppressive role of CD8+gammadelta T cells on allergic airway responses. However, only gammadelta T cells from naive donors inhibit LAR.
PubMed ID
13679814 View in PubMed
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EGF receptor activation during allergic sensitization affects IL-6-induced T-cell influx to airways in a rat model of asthma.

https://arctichealth.org/en/permalink/ahliterature97450
Source
Eur J Immunol. 2010 Jun;40(6):1590-602
Publication Type
Article
Date
Jun-2010
Author
Kimitake Tsuchiya
Taisuke Jo
Naoya Takeda
Saba Al Heialy
Sana Siddiqui
Karim Hamdy Shalaby
Paul-André Risse
Karim Maghni
James G Martin
Author Affiliation
Meakins-Christie Laboratories, McGill University, Montreal, QC, Canada.
Source
Eur J Immunol. 2010 Jun;40(6):1590-602
Date
Jun-2010
Language
English
Publication Type
Article
Keywords
Allergens - immunology
Animals
Asthma - immunology - metabolism
Blotting, Western
Bronchoalveolar Lavage Fluid - cytology - immunology
Cell Separation
Chemotaxis, Leukocyte - drug effects - immunology
Cytokines - biosynthesis
Disease Models, Animal
Enzyme Inhibitors - pharmacology
Flow Cytometry
Interleukin-6 - immunology
Lung - drug effects - immunology
Ovalbumin - immunology
Rats
Rats, Inbred BN
Receptor, Epidermal Growth Factor - immunology - metabolism
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes - drug effects - immunology
Tyrphostins - pharmacology
Abstract
EGF receptor (EGFR) is involved in cell differentiation and proliferation in airways and may trigger cytokine production by T cells. We hypothesized that EGFR inhibition at the time of allergic sensitization may affect subsequent immune reactions. Brown Norway rats were sensitized with OVA, received the EGFR tyrosine kinase inhibitor, AG1478 from days 0 to 7 and OVA challenge on day 14. OVA-specific IgE in serum and cytokines and chemokines in BAL were measured 24 h after challenge. To evaluate effects on airway hyperresponsiveness (AHR), rats were sensitized, treated with AG1478, intranasally challenged, and then AHR was assessed. Furthermore chemotactic activity of BALF for CD4(+) T cells was examined. The eosinophils, neutrophils and lymphocytes in BAL were increased by OVA and only the lymphocytes were reduced by AG1478. OVA significantly enhanced IL-6 concentration in BAL, which was inhibited by AG1478. However AHR, OVA-specific IgE and IL-4 mRNA expression in CD4(+) T cells were not affected by AG1478. BALF from OVA-sensitized/challenged rats induced CD4(+) T-cell migration, which was inhibited by both AG1478 treatment in vivo and neutralization of IL-6 in vitro. EGFR activation during sensitization may affect the subsequent influx of CD4(+) T cells to airways, mainly mediated through IL-6.
PubMed ID
20373517 View in PubMed
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Genetic influences on asthma susceptibility in the developing lung.

https://arctichealth.org/en/permalink/ahliterature100646
Source
Am J Respir Cell Mol Biol. 2010 Dec;43(6):720-30
Publication Type
Article
Date
Dec-2010
Author
Nicole Carpe
Isabel Mandeville
Leslie Ribeiro
Andre Ponton
James G Martin
Alvin T Kho
Jen-Hwa Chu
Kelan Tantisira
Scott T Weiss
Benjamin A Raby
Feige Kaplan
Author Affiliation
Department of Human Genetics, McGill University, 4060 Saint Catherine West, Montreal, PQ, Canada.
Source
Am J Respir Cell Mol Biol. 2010 Dec;43(6):720-30
Date
Dec-2010
Language
English
Publication Type
Article
Keywords
Active Transport, Cell Nucleus - genetics
Animals
Animals, Newborn
Antigens, Ly - genetics - metabolism
Asthma - genetics - pathology - physiopathology
Bronchoalveolar Lavage Fluid - cytology
Cell Nucleus - metabolism
Cell Proliferation
Female
Gene Expression Profiling
Gene Expression Regulation, Developmental
Genetic Predisposition to Disease
Goblet Cells - metabolism - pathology
Hyperplasia
Immunity, Innate - genetics
Leukocyte Count
Lung - enzymology - growth & development - pathology - physiopathology
Male
Rats
Respiratory Function Tests
Time Factors
Up-Regulation - genetics
Abstract
Asthma is the leading serious pediatric chronic illness in the United States, affecting 7.1 million children. The prevalence of asthma in children under 4 years of age has increased dramatically in the last 2 decades. Existing evidence suggests that this increase in prevalence derives from early environmental exposures acting on a pre-existing asthma-susceptible genotype. We studied the origins of asthma susceptibility in developing lung in rat strains that model the distinct phenotypes of airway hyperresponsiveness (Fisher rats) and atopy (brown Norway [BN] rats). Postnatal BN rat lungs showed increased epithelial proliferation and tracheal goblet cell hyperplasia. Fisher pups showed increased lung resistance at age 2 weeks, with elevated neutrophils throughout the postnatal period. Diverse transcriptomic signatures characterized the distinct respiratory phenotypes of developing lung in both rat models. Linear regression across age and strain identified developmental variation in expression of 1,376 genes, and confirmed both strain and temporal regulation of lung gene expression. Biological processes that were heavily represented included growth and development (including the T Box 1 transcription factor [Tbx5], the epidermal growth factor receptor [Egfr], the transforming growth factor beta-1-induced transcript 1 [Tgfbr1i1]), extracellular matrix and cell adhesion (including collagen and integrin genes), and immune function (including lymphocyte antigen 6 (Ly6) subunits, IL-17b, Toll-interacting protein, and Ficolin B). Genes validated by quantitative RT-PCR and protein analysis included collagen III alpha 1 Col3a1, Ly6b, glucocorticoid receptor and Importin-13 (specific to the BN rat lung), and Serpina1 and Ficolin B (specific to the Fisher lung). Innate differences in patterns of gene expression in developing lung that contribute to individual variation in respiratory phenotype are likely to contribute to the pathogenesis of asthma.
PubMed ID
20118217 View in PubMed
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IFN-gamma secretion by CD8T cells inhibits allergen-induced airway eosinophilia but not late airway responses.

https://arctichealth.org/en/permalink/ahliterature15380
Source
J Allergy Clin Immunol. 2002 May;109(5):803-9
Publication Type
Article
Date
May-2002
Author
Masaru Suzuki
Karim Maghni
Sophie Molet
Ayako Shimbara
Qutayba A Hamid
James G Martin
Author Affiliation
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Source
J Allergy Clin Immunol. 2002 May;109(5):803-9
Date
May-2002
Language
English
Publication Type
Article
Keywords
Adoptive Transfer
Allergens - immunology
Animals
Bronchi - immunology
Bronchial Hyperreactivity - immunology - physiopathology
Bronchitis - immunology - pathology
Bronchoalveolar Lavage Fluid - chemistry - cytology
CD8-Positive T-Lymphocytes - drug effects - metabolism - transplantation
Eosinophilia - immunology - prevention & control
Interferon Type II - physiology
Male
Oligonucleotides, Antisense - pharmacology
Ovalbumin - immunology
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Time Factors
Abstract
BACKGROUND: CD8+T cells can suppress allergen-induced late airway responses (LARs) and airway inflammation. OBJECTIVE: To test the hypothesis that the suppression of LARs and airway eosinophilia by CD8+T cells is IFN-gamma mediated, we tested the effects of adoptively transferred CD8+T cells, in which IFN-gamma synthesis was inhibited by an antisense (AS) oligodeoxynucleotide (ODN), on the airway responses of a rat model of allergic asthma. METHODS: CD8+T cells were harvested from the cervical lymph nodes of ovalbumin (OVA)-sensitized Brown Norway rats for administration to other actively sensitized syngeneic rats. CD8+T cells (2 x 10(6)) were incubated for 6 hours with 2 micromol/L AS ODN or sense ODN and were injected intraperitoneally into recipients; inhibition of IFN-gamma expression in vitro by AS ODN was shown by means of flow cytometry. Two days later, rats were challenged with aerosolized OVA. RESULTS: OVA-induced LAR and bronchoalveolar lavage (BAL) fluid eosinophilia were suppressed by sense ODN-treated CD8+T cells. IFN-gamma expression in BAL cells was elevated in these animals. IFN-gamma expression in BAL cells was at control levels in recipients of AS ODN-treated CD8+ cells, confirming the success of the AS treatment in vivo. BAL eosinophilia was also largely restored in the AS ODN treatment group. In contrast, the CD8+T cell-induced suppression of the LAR was not significantly affected by AS ODN pretreatment. CONCLUSIONS: These results indicate that CD8+T cells inhibit airway eosinophilia through secretion of IFN-gamma but may suppress the LAR by means of other mechanisms.
PubMed ID
11994704 View in PubMed
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Resident CD8+ T cells suppress CD4+ T cell-dependent late allergic airway responses.

https://arctichealth.org/en/permalink/ahliterature57383
Source
J Allergy Clin Immunol. 2005 Mar;115(3):521-6
Publication Type
Article
Date
Mar-2005
Author
Susumu Isogai
Sean Jedrzkiewicz
Rame Taha
Qutayba Hamid
James G Martin
Author Affiliation
Meakins Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec, Canada.
Source
J Allergy Clin Immunol. 2005 Mar;115(3):521-6
Date
Mar-2005
Language
English
Publication Type
Article
Keywords
Adoptive Transfer
Animals
Bronchoalveolar Lavage Fluid - cytology - immunology
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - immunology
Flow Cytometry
Immunohistochemistry
In Situ Hybridization
Interferon Type II - immunology
Interleukin-4 - immunology
Interleukin-5 - immunology
Ovalbumin - immunology
RNA, Messenger
Rats
Research Support, Non-U.S. Gov't
Respiratory Hypersensitivity - immunology
Abstract
BACKGROUND: The role of CD8+ T cells in the immune response to airway challenge with an allergen is poorly understood. OBJECTIVE: The aim of this study was to test the hypothesis that resident naive CD8+ T cells modulate the magnitude of CD4+ T cell-dependent allergic airway responses. METHODS: Cervical lymph node CD4+ T cells (2 x 10(6)) were harvested from ovalbumin (OVA)- or sham-sensitized rats and injected intraperitoneally into naive Brown Norway recipients. The recipients were treated with a CD8alpha mAb (OX-8) to deplete the resident CD8+ T cells (n = 12) or mouse ascites (n = 12). Two days after adoptive transfer, the recipient animals were OVA challenged, lung resistance was measured for 8 hours, and bronchoalveolar lavage (BAL) was performed. RESULTS: After OVA challenge, primed CD4-transferred CD8-depleted rats had larger early airway responses and late airway responses compared with primed CD4-transferred CD8-nondepleted rats (early airway responses: 158.6% +/- 19.2% vs 115.7% +/- 5.9%, P
PubMed ID
15753899 View in PubMed
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7 records – page 1 of 1.