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Complement Activation Is Critical to Airway Hyperresponsiveness after Acute Ozone Exposure

Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center; Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado; Protein Chemistry Laboratory, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; and The Jackson Laboratory, Bar Harbor, Maine

Correspondence and requests for reprints should be addressed to Erwin W. Gelfand, M.D., National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206. E-mail: gelfande{at}njc.org

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.

Key Words: ozone • complement activation • airway hyperresponsiveness

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