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 4

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Contribution of C5 at checkpoint 2, the development of AHR. C5s BALB/c m...
Contribution of C5 at checkpoint 2, the development of AHR. C5s BALB/c mice (A and B) and C5d B10D2.oSn mice (C and D) were immunized with OVA in as demonstrated in checkpoint 2 experiments in Figure 2B. Animals were randomized and given the indicated treatment i.p. on day 33. On day 35, aerosol Mch challenges were administered through a trachea cannula during measurement of RL (A and C) and Cdyn (B and D). Changes in RL and Cdyn are expressed as a percentage of baseline after each aerosol challenge. Subgroups of C5d mice with or without OVA immunization were reconstituted i.v. with 200 μg of rmC5a 3 hours prior to Mch challenges. For C5s BALB/c mice (A and B), *P < 0.05, steroid- or anti-C5 mAb–treated compared with control mAb-treated mice; for C5d B10D2.oSn mice (C and D), #P < 0.05, mice treated with mAb (n = 6: control mAb, n = 3; anti-C5 mAb, n = 3) compared with OVA-immunized mice reconstituted with rmC5a. There were no statistical differences between C5d animals treated with control mAb and anti-C5 mAb.