Complement Activation Is Critical to Airway Hyperresponsiveness after Acute Ozone Exposure

Jung Won Park, Christian Taube, Anthony Joetham, Katsuyuki Takeda, Taku Kodama, Azzeddine Dakhama, Glen McConville, Corrie B. Allen, Georgia Sfyroera, Lenny D. Shultz, John D. Lambris, Patricia C. Giclas, V. Michael Holers, Erwin W. Gelfand

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)


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 O 3 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.

Original languageEnglish
Pages (from-to)726-732
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number6
Publication statusPublished - 2004 Mar 15

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine


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