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Published ahead of print on September 18, 2003, doi:10.1164/rccm.200306-739OC
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American Journal of Respiratory and Critical Care Medicine Vol 168. pp. 1333-1341, (2003)
© 2003 American Thoracic Society

Inhibition of Complement Activation Decreases Airway Inflammation and Hyperresponsiveness

Christian Taube*, Yeong-Ho Rha*,{dagger},, Katsuyuki Takeda, Jung-Won Park, Anthony Joetham, Annette Balhorn, Azzeddine Dakhama, Patricia C. Giclas, V. Michael Holers and Erwin W. Gelfand

Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center; and Department of Medicine, Division of Rheumatology, University of Colorado Health Sciences Center, Denver, Colorado

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

Studies in murine models have suggested the involvement of the complement anaphylatoxins (C3a and C5a) in the development of allergic asthma. We investigated the effects of inhibiting complement activation after sensitization but before allergen challenge on the development of allergic airway inflammation and airway hyperresponsiveness. To prevent complement activation, we used a recombinant soluble form of the mouse membrane complement inhibitor complement receptor-related gene y (Crry) fused to the IgG1 hinge, CH2 and CH3 domains (Crry-Ig), which has decay-accelerating activity for both the classic and alternative pathways of complement as well as cofactor activity for factor I-mediated cleavage of C3b and C4b. C57BL/6 mice were sensitized (Days 1 and 14) and challenged (Days 24–26) with ovalbumin. Crry-Ig was administered after allergen sensitization either as an intraperitoneal injection or by nebulization before allergen challenge. Crry-Ig significantly prevented the development of airway hyperresponsiveness, decreased airway and lung eosinophilia as well as the numbers of lung lymphocytes, decreased levels of interleukin (IL)-4, IL-5, and IL-13 in bronchoalveolar lavage fluid and decreased serum ovalbumin-specific IgE and IgG1. These results suggest that prevention of complement activation may have a therapeutic role in the treatment of allergic airway inflammation and asthma in sensitized individuals.

Key Words: mouse model • lung function • lymphocytes • cytokines




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