Published ahead of print on February 1, 2007, doi:10.1164/rccm.200609-1260OC
Am. J. Respir. Crit. Care Med., Volume 175, Number 9, May 2007, 896-904
A more recent version of this article appeared on May 1, 2007
Submitted on September 4, 2006
Accepted on February 1, 2007
Remodelling and AHR but not Cellular Inflammation Persist After Allergen Challenge in Asthma
Harsha H Kariyawasam1, Maxine Aizen2, Julia Barkans2, Douglas S Robinson1, and A. Barry Kay3*
1 Allergy and Clinical Immunology Section, Imperial College London, National Heart and Lung Institute, London, United Kingdom; Leukocyte Biology Section, Imperial College London, National Heart and Lung Institute, London, United Kingdom; MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, National Heart and Lung Institute, London, United Kingdom,
2 Allergy and Clinical Immunology Section, Imperial College London, National Heart and Lung Institute, London, United Kingdom; MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, National Heart and Lung Institute, London, United Kingdom,
3 Leukocyte Biology Section, Imperial College London, National Heart and Lung Institute, London, United Kingdom; MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, Imperial College London, National Heart and Lung Institute, London, United Kingdom
* To whom correspondence should be addressed. E-mail: a.b.kay{at}imperial.ac.uk.
Rationale. Airway hyper-responsiveness increases up to 2 weeks after allergen inhalational challenge of asthmatics who show a late phase asthmatic reaction (dual responders). Cellular inflammation and airway remodelling are increased 24 hours after allergen challenge.
Objectives. To determine whether persistence of increased AHR is associated with persistent activation of remodelling and enhanced inflammation. Methods. Fibreoptic bronchoscopy was performed at baseline and at 24 hours and 7 days following allergen inhalational challenge of mild-moderate asthmatic dual responders. At each time point airway hyper-responsiveness, spirometry and expression of tenascin (extracellular matrix protein), procollagen I, procollagen III and HSP-47 (markers of collagen synthesis) and -smooth muscle actin (myofibroblasts) were evaluated as markers of activation of airway remodelling, together with numbers of mucosal MBP+ eosinophils, CD68+macrophages, CD3+, CD4+, CD8+ T cells, elastase+ neutrophils and tryptase+ mast cells. Measurements and Main Results. Airway hyper-responsiveness was increased from baseline at 24 hours and 7 days after allergen challenge. Reticular basement membrane (RBM) tenascin expression was elevated at 24 hours and returned to baseline levels at 7 days. RBM procollagen III expression was significantly elevated at 7 days. Expression of procollagen I, HSP-47 and alpha-smooth muscle actin were all higher at 7 days compared to 24 hours. At 24 hours eosinophil, macrophage, neutrophil and CD3+ T cells were increased but had returned to baseline by 7 days. Conclusion. In dual asthmatic responders the 24 hour increase in airway wall cellular inflammation after allergen challenge resolves by 7 days whereas the increases in AHR and markers of remodelling persist.
Key words: asthma, airway hyper-responsiveness (AHR), inflammation
This article has been cited by other articles:

|
 |

|
 |
 
M.-T. Huang, Y.-S. Dai, Y.-B. Chou, Y.-H. Juan, C.-C. Wang, and B.-L. Chiang
Regulatory T Cells Negatively Regulate Neovasculature of Airway Remodeling via DLL4-Notch Signaling
J. Immunol.,
October 1, 2009;
183(7):
4745 - 4754.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Semitekolou, T. Alissafi, M. Aggelakopoulou, E. Kourepini, H. H. Kariyawasam, A. B. Kay, D. S. Robinson, C. M. Lloyd, V. Panoutsakopoulou, and G. Xanthou
Activin-A induces regulatory T cells that suppress T helper cell immune responses and protect from allergic airway disease
J. Exp. Med.,
August 3, 2009;
206(8):
1769 - 1785.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. M. Tarlo, J.-L. Malo, and on behalf of the Third Jack Pepys Workshop on Asth
An Official ATS Proceedings: Asthma in the Workplace: The Third Jack Pepys Workshop on Asthma in the Workplace: Answered and Unanswered Questions
Proceedings of the ATS,
August 1, 2009;
6(4):
339 - 349.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. C. M. Simoes, G. Xanthou, K. Petrochilou, V. Panoutsakopoulou, C. Roussos, and C. Gratziou
Osteopontin Deficiency Protects against Airway Remodeling and Hyperresponsiveness in Chronic Asthma
Am. J. Respir. Crit. Care Med.,
May 15, 2009;
179(10):
894 - 902.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. A. Doherty, P. Soroosh, D. H. Broide, and M. Croft
CD4+ cells are required for chronic eosinophilic lung inflammation but not airway remodeling
Am J Physiol Lung Cell Mol Physiol,
February 1, 2009;
296(2):
L229 - L235.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Hewitt, A. Creel, K. Estell, I. C. Davis, and L. M. Schwiebert
Acute Exercise Decreases Airway Inflammation, but Not Responsiveness, in an Allergic Asthma Model
Am. J. Respir. Cell Mol. Biol.,
January 1, 2009;
40(1):
83 - 89.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. S. Cowburn, A. M. Condliffe, N. Farahi, C. Summers, and E. R. Chilvers
Advances in Neutrophil Biology: Clinical Implications
Chest,
September 1, 2008;
134(3):
606 - 612.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
W. C. Moore
Update in Asthma 2007
Am. J. Respir. Crit. Care Med.,
May 15, 2008;
177(10):
1068 - 1073.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. H. Kariyawasam, G. Xanthou, J. Barkans, M. Aizen, A. B. Kay, and D. S. Robinson
Basal Expression of Bone Morphogenetic Protein Receptor Is Reduced in Mild Asthma
Am. J. Respir. Crit. Care Med.,
May 15, 2008;
177(10):
1074 - 1081.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. von Garnier, M. E. Wikstrom, G. Zosky, D. J. Turner, P. D. Sly, M. Smith, J. A. Thomas, S. R. Judd, D. H. Strickland, P. G. Holt, et al.
Allergic Airways Disease Develops after an Increase in Allergen Capture and Processing in the Airway Mucosa
J. Immunol.,
November 1, 2007;
179(9):
5748 - 5759.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2007 American Thoracic Society
|
|
|