Published ahead of print on January 26, 2006, doi:10.1164/rccm.200503-334OC Am. J. Respir. Crit. Care Med., Volume 173, Number 8, April 2006, 852-857 A more recent version of this article appeared on April 15, 2006
Submitted on March 2, 2005 A Protective Role for the Fifth Complement Component (C5) in Allergic Airway DiseaseScott M Drouin1,1 The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX, USA, 2 Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA, 3 The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX, USA; Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston, Houston, TX, USA * To whom correspondence should be addressed. E-mail: Rick.A.Wetsel{at}uth.tmc.edu.
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 C5-deficiency 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 their wild-type congenic controls 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 IL-4-producing cells, respectively, compared to 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 antigen-specific 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. Key words: Complement, T Lymphocytes, TH1/TH2 Cells, Allergy, Lung
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