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

13 Citations (Scopus)

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

Fingerprint

Properdin
Inflammation
Bronchoalveolar Lavage
Allergens
Asthma
Alternative Complement Pathway
Methacholine Chloride
Eosinophils
Cell Count
Cytokines

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Wang, Y., Miwa, T., Ducka-Kokalari, B., Redai, I. G., Sato, S., Gullipalli, D., ... 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

Properdin contributes to allergic airway inflammation through local C3a generation. / Wang, Yuan; Miwa, Takashi; Ducka-Kokalari, Blerina; Redai, Imre G.; Sato, Sayaka; Gullipalli, Damodar; Zangrilli, James G.; Haczku, Angela Franciska; Song, Wen Chao.

In: Journal of Immunology, Vol. 195, No. 3, 01.08.2015, p. 1171-1181.

Research output: Contribution to journalArticle

Wang, Y, Miwa, T, Ducka-Kokalari, B, Redai, IG, Sato, S, Gullipalli, D, Zangrilli, JG, Haczku, AF & Song, WC 2015, 'Properdin contributes to allergic airway inflammation through local C3a generation', Journal of Immunology, vol. 195, no. 3, pp. 1171-1181. https://doi.org/10.4049/jimmunol.1401819
Wang Y, Miwa T, Ducka-Kokalari B, Redai IG, Sato S, Gullipalli D et al. Properdin contributes to allergic airway inflammation through local C3a generation. Journal of Immunology. 2015 Aug 1;195(3):1171-1181. https://doi.org/10.4049/jimmunol.1401819
Wang, Yuan ; Miwa, Takashi ; Ducka-Kokalari, Blerina ; Redai, Imre G. ; Sato, Sayaka ; Gullipalli, Damodar ; Zangrilli, James G. ; Haczku, Angela Franciska ; Song, Wen Chao. / Properdin contributes to allergic airway inflammation through local C3a generation. In: Journal of Immunology. 2015 ; Vol. 195, No. 3. pp. 1171-1181.
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