Inhibition of complement activation decreases airway inflammation and hyperresponsiveness.
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.
D000818:Animals; D001985:Bronchial Provocation Tests; D003170:Complement Pathway, Alternative / Q000187:drug effects*; D003171:Complement Pathway, Classical / Q000187:drug effects*; D004195:Disease Models, Animal; D005260:Female; D007074:Immunoglobulin G / Q000008:administration & dosage*; D007249:Inflammation / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D011506:Proteins / Q000008:administration & dosage*; D011951:Receptors, Complement / Q000008:administration & dosage*; D017463:Receptors, Complement 3b; D012130:Respiratory Hypersensitivity / Q000188:drug therapy*
C081470:Cr1l protein, mouse; D007074:Immunoglobulin G; D011506:Proteins; D011951:Receptors, Complement; D017463:Receptors, Complement 3b