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 language | English (US) |
|---|---|
| Pages (from-to) | 1171-1181 |
| Number of pages | 11 |
| Journal | Journal of Immunology |
| Volume | 195 |
| Issue number | 3 |
| DOIs | |
| State | Published - Aug 1 2015 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
- Medicine(all)
Cite this
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 journal › Article
}
TY - JOUR
T1 - Properdin contributes to allergic airway inflammation through local C3a generation
AU - Wang, Yuan
AU - Miwa, Takashi
AU - Ducka-Kokalari, Blerina
AU - Redai, Imre G.
AU - Sato, Sayaka
AU - Gullipalli, Damodar
AU - Zangrilli, James G.
AU - Haczku, Angela Franciska
AU - Song, Wen Chao
PY - 2015/8/1
Y1 - 2015/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84937705037&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84937705037&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1401819
DO - 10.4049/jimmunol.1401819
M3 - Article
C2 - 26116506
AN - SCOPUS:84937705037
VL - 195
SP - 1171
EP - 1181
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 3
ER -