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.

• Authors: Yuan Wang, Takashi Miwa, Blerina Ducka-Kokalari, Imre G Redai, Sayaka Sato, Damodar Gullipalli, James G Zangrilli, Angela Haczku, Wen-Chao Song
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 195 Issue 3 Pg. 1171-81 (Aug 01 2015) ISSN: 1550-6606 [Electronic] United States
• PMID: 26116506 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2015 by The American Association of Immunologists, Inc.

Chemical References

• Methacholine Chloride
• Properdin
• Complement C3a

Topics

• Animals
• Asthma (chemically induced, immunology, pathology)
• Bronchoalveolar Lavage Fluid (chemistry, cytology)
• Complement C3a (biosynthesis, immunology)
• Eosinophils (immunology)
• Humans
• Inflammation (immunology)
• Leukocyte Count
• Lung (immunology, pathology)
• Methacholine Chloride (pharmacology)
• Mice
• Mice, Inbred C57BL
• Properdin (genetics, immunology)
• Th17 Cells (immunology)
• Th2 Cells (immunology)