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Role of airway smooth muscle in airway remodeling

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Presentation on theme: "Role of airway smooth muscle in airway remodeling"— Presentation transcript:

1 Role of airway smooth muscle in airway remodeling
Philippe Joubert, DVM, MSc, Qutayba Hamid, MD, PhD  Journal of Allergy and Clinical Immunology  Volume 116, Issue 3, Pages (September 2005) DOI: /j.jaci Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

2 Fig 1 Increase in smooth muscle mass in the large airway of a subject with severe asthma. Hematoxylin and eosin staining; magnification 200×. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

3 Fig 2 Increase in smooth muscle mass in the small airway of a subject with severe asthma. Hematoxylin and eosin staining; magnification 200×. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

4 Fig 3 Hematoxylin and eosin preparation from a biopsy specimen of an asthmatic subject shows smooth muscle bundles close to the epithelium. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

5 Fig 4 Model representing the migration of ASMCs toward the epithelium, possibly mediated by chemokines. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

6 Fig 5 ASMCs express a wide variety of mediators involved in asthma pathogenesis, including cytokines, chemokines, growth factors, and lipid mediators. LIF, leukocyte inhibitory factor; TARC, thymus- and activation-regulated chemokine; PDGF, platelet-derived growth factor; PGE2, prostaglandin E2; SCF, stem cell factor; VEGF, vascular endothelial growth factor; ADAM, a disintegrin and metalloprotease; PLA2, phospholipase A2. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

7 Fig 6 Example of the potential of ASMCs to produce cytokines and chemokines. Protein array of supernatant obtained from ASMCs shows immunoreactivity (in red in the table) to a number of cytokines and chemokines. Pos, Positive; Neg, negative; MCSF, macrophage colony-stimulating factor; IGF-1, insulin-like growth factor 1; MDC, macrophage-derived chemotactic factor; Ang, angiopoietin; GCSF, granulocyte colony-stimulating factor; MIG, monokine induced by IFN-γ; OSM, oncostatin M; GRO, growth-related oncogene; VEGF, vascular endothelial growth factor; SCF, stem cell factor; PDGF, platelet-derived growth factor; SDF-1, stromal cell-derived factor-1; TARC, thymus- and activation-regulated cytokine. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

8 Fig 7 CCR3 immunostaining from a biopsy specimen of an asthmatic subject shows positive signal in smooth muscle bundles. Diaminobenzidine method; magnification 400×. Epith, Epithelium. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

9 Fig 8 Flow cytometric analysis of cultured ASMCs with an anti-CCR1 coupled with phycoerythrin. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

10 Fig 9 Western blotting and real-time PCR analysis of extracellular matrix protein production by cultured ASMCs. Lumican production was assessed after stimulation with different cytokines for 48 hours, and versican production was evaluated after stimulation with IL-25 in a time-dependent manner. Messenger RNA collagen production was quantified by using real-time PCR after 24 hours of stimulation with TFG-β. BL, baseline. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

11 Fig 10 Example of a laser capture microdissection of ASMCs in a biopsy specimen obtained from an asthmatic subject. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

12 Fig 11 RT-PCR for CCL15 expression performed on mRNA extracted from laser capture microdissection on biopsy specimens from asthmatic subjects. Ctrl, Control. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2005 American Academy of Allergy, Asthma and Immunology Terms and Conditions

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