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Complement Factor 3 Mediates Particulate Matter–Induced Airway Hyperresponsiveness

Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland; and Division of Immunobiology, Children's Hospital Medical Center, Cincinnati, Ohio

Address correspondence to: Marsha Wills-Karp, Ph.D., Division of Immunobiology, Children's Hospital Medical Center, 3333 Burnet Avenue, Rm. 1553, Cincinnati, OH 45229. E-mail: wildc7{at}chmcc.org

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.

Abbreviations: acetylcholine, ACh • airway hyperresponsiveness, AHR • bronchoalveolar lavage, BAL • complement factor 3, C3 • phosphate-buffered saline, PBS • particulate matter, PM

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