title: Complement activation is critical to airway hyperresponsiveness after acute ozone exposure.
abstract: Ozone (O3) can induce airway hyperresponsiveness (AHR) and neutrophilic inflammation. We evaluated the role of complement in development of AHR and inflammation after acute O3 exposure in mice. Mice were exposed to O3 at 2 ppm for 3 hours, and airway responsiveness to methacholine was measured 8 hours after O3 exposure. Complement was depleted or inhibited by intraperitoneal injection of cobra venom factor (CVF) or complement receptor-related gene y (Crry)-Ig, a potent C3 convertase inhibitor; neutrophils were depleted using an antineutrophil monoclonal antibody. CVF attenuated the development of AHR by O3. Administration of Crry-Ig also prevented the development of AHR. Bronchoalveolar lavage (BAL) fluid neutrophilia after O3 exposure was significantly decreased by administration of either CVF or Crry-Ig. Increased BAL fluid total protein after O3 exposure was lowered by depletion or inhibition of complement. In contrast to the effects of complement inhibition or depletion, depletion of BAL neutrophil counts by more than 90% with the monoclonal antibody did not affect the development of AHR after O3 exposure. These data indicated that activation of the complement system follows acute O3 exposure and is important to the development of AHR and airway neutrophilia. However, this neutrophil response does not appear necessary for the development of AHR.
authors.affiliation: Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
authors.forename: Jung-Won
authors.initials: JW
authors.lastname: Park
authors.forename: Christian
authors.initials: C
authors.lastname: Taube
authors.forename: Anthony
authors.initials: A
authors.lastname: Joetham
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Takeda
authors.forename: Taku
authors.initials: T
authors.lastname: Kodama
authors.forename: Azzeddine
authors.initials: A
authors.lastname: Dakhama
authors.forename: Glen
authors.initials: G
authors.lastname: McConville
authors.forename: Corrie B
authors.initials: CB
authors.lastname: Allen
authors.forename: Georgia
authors.initials: G
authors.lastname: Sfyroera
authors.forename: Lenny D
authors.initials: LD
authors.lastname: Shultz
authors.forename: John D
authors.initials: JD
authors.lastname: Lambris
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Giclas
authors.forename: V Michael
authors.initials: VM
authors.lastname: Holers
authors.forename: Erwin W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000503:physiopathology*; D003167:Complement Activation / Q000187:drug effects / Q000502:physiology*; D003169:Complement Inactivator Proteins / Q000494:pharmacology*; D004195:Disease Models, Animal; D004546:Elapid Venoms / Q000494:pharmacology*; D005260:Female; D007136:Immunoglobulins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018375:Neutrophil Activation / Q000502:physiology; D010083:Oxidants, Photochemical / Q000633:toxicity; D010126:Ozone / Q000633:toxicity; D011951:Receptors, Complement / Q000502:physiology*; D017463:Receptors, Complement 3b
chemical_list: D003169:Complement Inactivator Proteins; C081470:Cr1l protein, mouse; D004546:Elapid Venoms; D007136:Immunoglobulins; D010083:Oxidants, Photochemical; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; C016310:cobra venom factor; D010126:Ozone