Role of C5 in the development of airway inflammation, airway hyperresponsiveness, and ongoing airway response
Tao Peng, … , Stephen Squinto, Yi Wang
Tao Peng, … , Stephen Squinto, Yi Wang
Published June 1, 2005
Citation Information: J Clin Invest. 2005;115(6):1590-1600. https://doi.org/10.1172/JCI22906.
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Role of C5 in the development of airway inflammation, airway hyperresponsiveness, and ongoing airway response

Abstract

The role of complement component C5 in asthma remains controversial. Here we examined the contribution of C5 at 3 critical checkpoints during the course of disease. Using an mAb specific for C5, we were able to evaluate the contribution of C5 during (a) the initiation of airway inflammation, (b) the maintenance of airway hyperresponsiveness (AHR), and (c) sustainment of an ongoing airway response to allergen provocation. Our results indicate that C5 is probably activated intrapulmonarily after infections or exposures to allergen and C5 inhibition has profound effects at all 3 critical checkpoints. In contrast to an earlier report, C5-deficient mice with established airway inflammation did not have elevated AHR to nonspecific stimuli. In the presence of airway inflammation, C5a serves as a direct link between the innate immune system and the development of AHR by engaging directly with its receptors expressed in airways. Through their powerful chemotactic and cell activation properties, both C5a and C5b-9 regulate the downstream inflammatory cascade, which results in a massive migration of inflammatory cells into the bronchial airway lumen and triggers the release of multiple harmful inflammatory mediators. This study suggests that targeting C5 is a potential clinical approach for treating patients with asthma.

Authors

Tao Peng, Liming Hao, Joseph A. Madri, Xiao Su, Jack A. Elias, Gregory L. Stahl, Stephen Squinto, Yi Wang

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Figure 3

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Contribution of C5 at checkpoint 1, the initiation of airway inflammatio...
Contribution of C5 at checkpoint 1, the initiation of airway inflammation. (A) Mean serum OVA-specific antibody titers of 5–6 mice on day 32 were measured by ELISA. Gray bars: OVA-specific IgG; white bars: OVA-specific IgE. Also on day 32, animals were trachea cannulated for the measurement of RL (B) and Cdyn (C) 5 hours after 5% aerosol OVA provocation, which was followed by histological analyses of lung (D). The mean histology score for control mAb–treated mice (F) was 2 ± 0.28 compared with 0.64 ± 0.21 for corticosteroid-treated animals (G) and 1.25 ± 0.25 for anti-C5 mAb–treated animals (H) compared with the total lack of inflammation (score: 0) seen in sham-treated mice (E). *P < 0.05, corticosteroid- or anti-C5 mAb–treated compared with control mAb–treated mice; #P < 0.05, corticosteroid-treated mice compared with animals treated with anti-C5 mAb. For clarity, all control mAb–treated animals are labeled as control in all following figures. Arrow indicates eosinophil infiltration. Giemsa stain, magnification = ×100.