Complement activation is critical to airway hyperresponsiveness after acute ozone exposure.
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.
Park
Jung-Won
JW
Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Taube
Christian
C
Joetham
Anthony
A
Takeda
Katsuyuki
K
Kodama
Taku
T
Dakhama
Azzeddine
A
McConville
Glen
G
Allen
Corrie B
CB
Sfyroera
Georgia
G
Shultz
Lenny D
LD
Lambris
John D
JD
Giclas
Patricia C
PC
Holers
V Michael
VM
Gelfand
Erwin W
EW
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
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