A protective role for the fifth complement component (c5) in allergic airway disease.
BACKGROUND
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.


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 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.
Drouin
Scott M
SM
The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Sinha
Meenal
M
Sfyroera
Georgia
G
Lambris
John D
JD
Wetsel
Rick A
RA
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003167:Complement Activation / Q000502:physiology; D003176:Complement C3 / Q000172:deficiency; D003182:Complement C5 / Q000172:deficiency / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007155:Immunologic Factors / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D018418:Th2 Cells / Q000276:immunology; D016896:Treatment Outcome
D015415:Biomarkers; D003176:Complement C3; D003182:Complement C5; D007155:Immunologic Factors; D015847:Interleukin-4; D007371:Interferon-gamma