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A Protective Role for the Fifth Complement Component (C5) in Allergic Airway Disease
- Publication Year :
- 2006
- Publisher :
- American Thoracic Society, 2006.
-
Abstract
- Rationale: Reports from our laboratory, as well as those from others, have documented the importance of complement activation, the C3a anaphylatoxin, and its receptor, C3aR, in promoting Th2 effector functions in a mouse model of bronchopulmonary allergy. Although deficiency in the fifth complement component (C5) has been linked to enhanced airway hyperresponsiveness in mice, the contribution of C5 to other major biological hallmarks of asthma has not been evaluated. Objective: Accordingly, congenic C5-sufficient and C5-deficient mice were subjected to a mouse model of bronchopulmonary allergy to assess the impact of C5 on pulmonary inflammation and Th2 effector functions in experimental asthma. Methods and Main Results: In contrast to observations reported for C3- and C3aR-deficient animals, C5-deficient mice exhibited significantly increased airway hyperresponsiveness relative to wild-type congenic control mice after antigen challenge. Moreover, challenged C5-deficient mice had a 3.4-fold and 2.7-fold increase in the levels of airway eosinophils and lung interleukin (IL)-4–producing cells, respectively, compared with challenged wild-type mice. Consistent with the numbers of IL-4–producing cells, C5-deficient mice also had increased bronchoalveolar lavage levels of the Th2 cytokines IL-5 and IL-13 and elevated serum levels of total and antigenspecific IgE. Conclusions: These data indicate that C5 plays an important protective role in allergic lung disease by suppressing inflammatory responses and Th2 effector functions observed in this experimental model. The protection provided by the presence of C5 is likely mediated by C5a, suggesting that C5a may play a significant role in tempering inflammation in Th2-driven diseases such as asthma.
- Subjects :
- Pulmonary and Respiratory Medicine
Allergy
Inflammation
Enzyme-Linked Immunosorbent Assay
Critical Care and Intensive Care Medicine
Immunoglobulin E
B. Asthma and Allergy
Interferon-gamma
Mice
Th2 Cells
medicine
Respiratory Hypersensitivity
Animals
Immunologic Factors
Anaphylatoxin
Complement Activation
Lung
Interleukin 4
Complement component 5
biology
medicine.diagnostic_test
business.industry
Complement C5
Complement C3
medicine.disease
Complement system
Disease Models, Animal
Bronchoalveolar lavage
Treatment Outcome
Immunology
biology.protein
Interleukin-4
medicine.symptom
business
Biomarkers
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....38362dd198c359152db94646aaa5687a