Mycobacterium tuberculosis Chaperonin 60.1 Inhibits Leukocyte Diapedesis in a Murine Model of Allergic Lung Inflammation
Autor: | Anthony R.M. Coates, Domenico Spina, Yanira Riffo-Vasquez, Clive P. Page |
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Rok vydání: | 2012 |
Předmět: |
Male
Pulmonary and Respiratory Medicine Ovalbumin Clinical Biochemistry Anti-Inflammatory Agents Inflammation Pharmacology Mycobacterium tuberculosis Mice Leukocytes medicine Animals Molecular Biology Mice Knockout Mice Inbred BALB C Lung biology medicine.diagnostic_test Chaperonin 60 Pneumonia Cell Biology respiratory system medicine.disease biology.organism_classification Interleukin-12 Eosinophils Mice Inbred C57BL Toll-Like Receptor 4 Disease Models Animal medicine.anatomical_structure Bronchoalveolar lavage Bronchial hyperresponsiveness Immunology biology.protein Female Nasal administration Bronchial Hyperreactivity Interleukin-5 medicine.symptom Bronchoalveolar Lavage Fluid Cell Adhesion Molecules Intravital microscopy |
Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 47:245-252 |
ISSN: | 1535-4989 1044-1549 |
Popis: | Chaperonin 60.1 from Mycobacterium tuberculosis suppressed allergic lung inflammation and bronchial hyperresponsiveness in mice by a mechanism that is yet to be clarified. To investigate the possible antiinflammatory mechanism(s) of action of Cpn60.1 in a model of allergic lung inflammation, ovalbumin (OVA)-allergic mice were pretreated with Cpn60.1 intranasally 20 minutes before each OVA aerosol challenge in a total of three treatments. Readouts were performed 24 hours after last challenge. Pretreatment with Cpn60.1 (1.0-0.001 μg) significantly inhibited the number of eosinophils in bronchoalveolar lavage fluid (OVA, 49.2 ± 12.3 versus Cpn60.1 [1 μg dose], 90.4 ± 2.3 × 10(4) cells/ml) and IL-5 release (OVA, 43 ± 8.5 versus Cpn60.1 [1 μg dose], 3 ± 11 pg/ml) but increased IL-12 levels (OVA, 50 ± 24 versus Cpn60.1 [1 μg dose], 103 ± 13 pg/ml). The effect of Cpn60.1 on cell recruitment and IL-5, but not IL-12, release was abolished in TLR-4 knockout mice. Intravital microscopy demonstrated that Cpn60.1 reduced chemokine-mediated leukocyte rolling and transmigration across the vessel wall (rolling cells: eotaxin, 11.7 ± 1.1 versus Cpn60.1 [1 μg dose], 2.8 ± 1 cells in 30 s). Similarly, Cpn60.1 reduced eotaxin-induced leukocyte migration in vitro (eotaxin, 17.3 ± 3.3 versus Cpn60.1 [0.1 μg dose], 3.3 ± 0.4 cells × 10(4)/ml). Immunostaining demonstrated that Cpn60.1 inhibits VCAM-1 and increases vascular endothelial-cadherin expression in lung vascular tissue, suggesting that the antiinflammatory effect of Cpn60.1 is partly mediated by altering the expression of adhesion molecules. This study shows that Cpn60.1 inhibits leukocyte diapedesis by a TLR-4 and an adhesion molecule-dependent mechanism in allergic inflammation in mice. |
Databáze: | OpenAIRE |
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