Strain-related differences in Sephadex bead-induced airway hyperresponsiveness and inflammation in rats

Matsubara, Shigeki; Nakata, Aya; Kikuchi, Makoto; Kikkawa, Hideo; Ikezawa, Katsuo; Naito, Kunihiko

doi:10.1007/s000110050191

Cited by 10 publications

(10 citation statements)

References 22 publications

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“…Although the inhibitory mechanism of GCC is still not clear, the inhibition of the eosinophilia by the compound did not prevent the development of AHR. In our previous experiment, we could not find a correlation between the development of AHR and recruitment of eosinophils in the airways in four inbred rat strains [10]. Kubin et al [16] reported that intratracheal administration of Sephadex in Brown-Norway rats leads to pulmonary eosinophilia without AHR.…”

Section: Discussionmentioning

confidence: 99%

“…These findings show that the development of AHR is associated with the recruitment of eosinophils into the airway lumen. In our previous experiment [10], dexamethasone inhibited both AHR and increases in eosinophils and mononuclear cells, although the number of neutrophils was increased by dexamethasone in Sephadex-treated rats. However, protein exudation in BALF was not significantly prevented by dexamethasone in Sephadex-treated rats [10].…”

Section: Discussionmentioning

confidence: 99%

“…In our previous experiment [10], dexamethasone inhibited both AHR and increases in eosinophils and mononuclear cells, although the number of neutrophils was increased by dexamethasone in Sephadex-treated rats. However, protein exudation in BALF was not significantly prevented by dexamethasone in Sephadex-treated rats [10]. These findings suggest that increases in eosinophils and mononuclear cells, but not in neutrophils and protein exudation in BALF could be associated with the development of AHR induced by Sephadex.…”

Section: Discussionmentioning

confidence: 99%

“…We could not demonstrate reproducible AHR by Sephadex injection in Sprague-Dawley rats; the magnitude of AHR in the strain varied widely in our previous experiments [10]. In our previous report, we showed that the Lewis rat strain has exhibited significant AHR with pulmonary eosinophilia induced by Sephadex throughout the study, but Brown-Norway, Fischer 344 and Wistar-Kyoto rats did not [10]. There is no reported investigation of Sephadex-induced AHR and airway inflammation using Lewis rats.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Pulmonary Eosinophilia Does Not Necessarily Prevent the Airway Hyperresponsiveness Induced by Sephadex Beads

Matsubara

Fushimi

Ogawa

et al. 1998

Int Arch Allergy Immunol

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Background: The Lewis rat among highly inbred strains exhibits significant airway hyperresponsiveness (AHR) following intravenous administration of Sephadex G-200 (Sephadex). The aim of this study was to investigate the association of Sephadex-induced AHR with changes in airway inflammation in Lewis rats. Methods: A suspension (0.5 mg/ml/rat) of Sephadex was intravenously administered to male Lewis rats on days 0, 2 and 5. Measurement of airway responsiveness to serotonin, bronchoalveolar lavage (BAL) and histological study were performed on day 2–11. Results: Significant AHR induced by Sephadex was recognized on day 2 (p < 0.05), and AHR reached a maximum on day 7 (p < 0.001). In the BAL study, eosinophils increased on day 2 (p < 0.01) with a peak on day 5 (p < 0.05). In the histological study, we found Sephadex beads trapped in small arteries of the lung and granulomatous arteritis on day 2 or later. Pulmonary granulomas, horseshoe-shaped multinuclear giant cells, eosinophils and goblet cell hyperplasia were observed on day 2, and the degree became intense on day 5–7. GCC-AP0341 (10 mg/kg, i.p. × 3) inhibited the recruitment of eosinophils in BAL fluid and in lung tissue, but it did not inhibit AHR. The compound also inhibited pulmonary granulomas and goblet cell hyperplasia. Conclusion: The mechanism of Sephadex-induced AHR may not be directly associated with inflammatory changes such as recruitment of eosinophils, pulmonary granulomas and hyperplasia of goblet cells in rats.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhibition of Pulmonary Eosinophilia Does Not Necessarily Prevent the Airway Hyperresponsiveness Induced by Sephadex Beads

Matsubara

Fushimi

Ogawa

et al. 1998

Int Arch Allergy Immunol

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“…Reverse transcription. A 1-g portion of total RNA was subjected to first strand cDNA synthesis in a 25-l reaction mixture containing avian myeloblastosis virus reverse transcriptase (10 U), dNTP (2 mM concentrations of each dNTP), oligo(dT) [12][13][14][15][16][17][18] primers (10 M), and reaction buffer as supplied with the enzyme (50 mM Tris-HCl (pH 8.3), 50 mM KCl, 10 mM MgCl 2 , 0.5 mM spermidine, and 10 mM DTT). The samples were incubated in a PerkinElmer 480 thermal cycler (PerkinElmer, Wellesley, MA) at 42°C for 60 min followed by enzyme denaturation step at 94°C for 2 min.…”

Section: Lung Cytokine Gene Expression (Rt-pcr)mentioning

confidence: 99%

Critical Role for T Cells in Sephadex-Induced Airway Inflammation: Pharmacological and Immunological Characterization and Molecular Biomarker Identification

Haddad¹,

Underwood²,

Dabrowski

et al. 2002

The Journal of Immunology

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Intratracheal instillation of Sephadex particles is a convenient model for assessing the impact of potential anti-inflammatory compounds on lung eosinophilia thought to be a key feature in asthma pathophysiology. However, the underlying cellular and molecular mechanisms involved are poorly understood. We have studied the time course of Sephadex-induced lung eosinophilia, changes in pulmonary T cell numbers, and gene and protein expression as well as the immunological and pharmacological modulation of these inflammatory indices in the Sprague Dawley rat. Sephadex increased T cell numbers (including CD4+ T cells) and evoked a pulmonary eosinophilia that was associated with an increase in gene/protein expression of the Th2-type cytokines IL-4, IL-5, and IL-13 and eotaxin in lung tissue. Sephadex instillation also induced airway hyperreactivity to acetylcholine and bradykinin. A neutralizing Ab (R73) against the αβ-TCR caused 54% depletion of total (CD2+) pulmonary T cells accompanied by a significant inhibition of IL-4, IL-13 and eotaxin gene expression together with suppression (65% inhibition) of eosinophils in lung tissue 24 h after Sephadex treatment. Sephadex-induced eosinophilia and Th2 cytokine gene and/or protein expression were sensitive to cyclosporin A and budesonide, compounds that inhibit T cell function, suggesting a pivotal role for T cells in orchestrating Sephadex-induced inflammation in this model.

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Animal models of bronchial asthma

Szelenyi¹

2000

Inflammation Research

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Due to the continuous increase in prevalence and morbidity in asthma, there is an urgent need to improve present therapy by drugs with new modes of actions. In contrast to many human diseases, allergic asthma does not occur in the animal world. Therefore, we have to mimic some characteristic feature of asthma in animals. For this reason, a wide variety of animal models have been developed and are employed in the search for new chemical entities for asthma therapy. In the present paper, the experimental models of the most characteristic asthma symptoms are critically reviewed.

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Strain-related differences in Sephadex bead-induced airway hyperresponsiveness and inflammation in rats

Abstract: These results indicate that the Lewis rat is a useful strain for analysis of the mechanism of Sephadex-induced AHR and airway inflammation.

Cited by 10 publications

References 22 publications

Inhibition of Pulmonary Eosinophilia Does Not Necessarily Prevent the Airway Hyperresponsiveness Induced by Sephadex Beads

Inhibition of Pulmonary Eosinophilia Does Not Necessarily Prevent the Airway Hyperresponsiveness Induced by Sephadex Beads

Critical Role for T Cells in Sephadex-Induced Airway Inflammation: Pharmacological and Immunological Characterization and Molecular Biomarker Identification

Animal models of bronchial asthma

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