Properdin contributes to allergic airway inflammation through local C3a generation

Yuan Wang, Takashi Miwa, Blerina Ducka-Kokalari, Imre G. Redai, Sayaka Sato, Damodar Gullipalli, James G. Zangrilli, Angela Franciska Haczku, Wen Chao Song

Research output: Contribution to journalArticle

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1171-1181
Number of pages11
JournalJournal of Immunology
Volume195
Issue number3
DOIs
StatePublished - Aug 1 2015
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

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    Wang, Y., Miwa, T., Ducka-Kokalari, B., Redai, I. G., Sato, S., Gullipalli, D., Zangrilli, J. G., Haczku, A. F., & Song, W. C. (2015). Properdin contributes to allergic airway inflammation through local C3a generation. Journal of Immunology, 195(3), 1171-1181. https://doi.org/10.4049/jimmunol.1401819