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.