Complement factor 3 mediates particulate matter-induced airway hyperresponsiveness.
Epidemiologic studies have suggested that exposure to airborne particulate matter (PM) can exacerbate allergic airway responses; however, the mechanism(s) are not well understood. We and others have recently shown that development of airway hyperresponsiveness (AHR) may be a complement-mediated process. In the present study, we examined the role of complement factor 3 (C3) in the development of PM-induced AHR and airway inflammation by comparing responses between C3-deficient (C3(-/-)) and wild-type mice. Mice were exposed to 0.5 mg of ambient particulate collected in urban Baltimore. Forty-eight hours later, airway responsiveness to intravenous acetylcholine was assessed and bronchoalveolar lavage was conducted. PM exposure of wild-type mice resulted in significant increases in AHR, whereas it did not significantly increase airway reactivity in C3(-/-) mice. Interestingly, PM induced similar inflammatory responses in both wild-type and C3(-/-) mice. Immunohistochemical staining demonstrated marked C3 deposition in the airway epithelium and connective tissue of wild-type mice after PM exposure. These results suggest that exposure to PM may induce AHR through activation of complement factor 3 in the airways.
D000397:Air Pollution / Q000032:analysis; D000818:Animals; D001980:Bronchi / Q000276:immunology* / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D003176:Complement C3 / Q000378:metabolism* / Q000502:physiology*; D004804:Eosinophils / Q000473:pathology; D004847:Epithelial Cells / Q000473:pathology; D007150:Immunohistochemistry; D007249:Inflammation; D008168:Lung / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000473:pathology
D003176:Complement C3