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Properdin Contributes to Allergic Airway Inflammation through Local C3a Generation.


ABSTRACT: Complement is implicated in asthma pathogenesis, but its mechanism of action in this disease remains incompletely understood. In this study, we investigated the role of properdin (P), a positive alternative pathway complement regulator, in allergen-induced airway inflammation. Allergen challenge stimulated P release into the airways of asthmatic patients, and P levels positively correlated with proinflammatory cytokines in human bronchoalveolar lavage (BAL). High levels of P were also detected in the BAL of OVA-sensitized and challenged but not naive mice. Compared with wild-type (WT) mice, P-deficient (P(-/-)) mice had markedly reduced total and eosinophil cell counts in BAL and significantly attenuated airway hyperresponsiveness to methacholine. Ab blocking of P at both sensitization and challenge phases or at challenge phase alone, but not at sensitization phase alone, reduced airway inflammation. Conversely, intranasal reconstitution of P to P(-/-) mice at the challenge phase restored airway inflammation to wild-type levels. Notably, C3a levels in the BAL of OVA-challenged P(-/-) mice were significantly lower than in wild-type mice, and intranasal coadministration of an anti-C3a mAb with P to P(-/-) mice prevented restoration of airway inflammation. These results show that P plays a key role in allergen-induced airway inflammation and represents a potential therapeutic target for human asthma.

SUBMITTER: Wang Y 

PROVIDER: S-EPMC4506880 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Properdin Contributes to Allergic Airway Inflammation through Local C3a Generation.

Wang Yuan Y   Miwa Takashi T   Ducka-Kokalari Blerina B   Redai Imre G IG   Sato Sayaka S   Gullipalli Damodar D   Zangrilli James G JG   Haczku Angela A   Song Wen-Chao WC  

Journal of immunology (Baltimore, Md. : 1950) 20150626 3


Complement is implicated in asthma pathogenesis, but its mechanism of action in this disease remains incompletely understood. In this study, we investigated the role of properdin (P), a positive alternative pathway complement regulator, in allergen-induced airway inflammation. Allergen challenge stimulated P release into the airways of asthmatic patients, and P levels positively correlated with proinflammatory cytokines in human bronchoalveolar lavage (BAL). High levels of P were also detected i  ...[more]

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