Cutting edge: the absence of C3 demonstrates a role for complement in Th2 effector functions in a murine model of pulmonary allergy.
Asthma is a chronic disease of the lung resulting from airway obstruction. Although the initiating causes are not entirely clear, the airway inflammation in asthma is associated with Th2 lymphocytes and their cytokines, particularly IL-4, which play a prominent role in this disease by regulating airway hyperresponsiveness, eosinophil activation, and IgE synthesis. Historically, complement was not thought to contribute to the pathogenesis of asthma. However, using C3-deficient mice in an allergen-induced model of pulmonary allergy, we demonstrate that complement may impact key features of this disease. When challenged with allergen, mice deficient in C3 exhibit diminished airway hyperresponsiveness and lung eosinophilia. Furthermore, these mice also have dramatically reduced numbers of IL-4-producing cells and attenuated Ag-specific IgE and IgG1 responses. Collectively, these results demonstrate that C3-deficient mice have significantly altered allergic lung responses and indicate a role for the complement system in promoting Th2 effector functions in asthma.
Drouin
S M
SM
Institute of Molecular Medicine for the Prevention of Human Diseases, Department of Biochemistry and Molecular Biology, University of Texas, Houston, TX 77030, USA.
Corry
D B
DB
Kildsgaard
J
J
Wetsel
R A
RA
D000818:Animals; D000918:Antibody Specificity; D001249:Asthma / Q000209:etiology / Q000276:immunology*; D003176:Complement C3 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D006967:Hypersensitivity / Q000209:etiology / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008168:Lung / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D011657:Pulmonary Eosinophilia; D018418:Th2 Cells / Q000276:immunology*
D003176:Complement C3; D007074:Immunoglobulin G; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma