Document Detail

Serum amyloid A promotes lung neutrophilia by increasing IL-17A levels in the mucosa and γδ T cells.
MedLine Citation:
PMID:  23627303     Owner:  NLM     Status:  MEDLINE    
RATIONALE: Neutrophilic inflammation is an important pathologic feature of chronic obstructive pulmonary disease (COPD) and infectious exacerbations of COPD. Serum amyloid A (SAA) promotes neutrophilic inflammation by its interaction with lung mucosal ALX/FPR2 receptors. However, little is known about how this endogenous mediator regulates IL-17A immunity.
OBJECTIVES: To determine whether SAA causes neutrophilic inflammation by IL-17A-dependent mechanisms.
METHODS: The relationship between SAA and neutrophils was investigated in lung sections from patients with COPD and a chronic mouse model of SAA exposure. A neutralizing antibody to IL-17A was used to block SAA responses in vivo, and a cell-sorting strategy was used to identify cellular sources.
MEASUREMENTS AND MAIN RESULTS: SAA mRNA expression was positively associated with tissue neutrophils in COPD (P < 0.05). SAA predominately promoted expression of the TH17 polarizing cytokine IL-6, which was opposed by 15-epi-lipoxin A4, a counter-regulatory mediator, and ALX/FPR2 ligand. SAA-induced inflammation was markedly reduced by a neutralizing antibody to IL-17A in vivo. Cellular sources of IL-17A induced by SAA include CD4(+) T cells, γδ T cells, and an Epcam(+)CD45(-) population enriched for epithelial cells. SAA promotes expression of IL-17A in γδ T cells and this innate cell proportionally expressed higher levels of IL-17A transcript than CD4(+) T cells or epithelial cells.
CONCLUSIONS: The SAA-IL-17A axis represents an important innate defense network that may underlie persistent neutrophilic airway inflammation in COPD and modulating the ALX/FPR2 receptor represents a novel approach to targeting aberrant IL-17A-mediated lung immunity.
Desiree Anthony; Huei Jiunn Seow; Mohib Uddin; Michelle Thompson; Lovisa Dousha; Ross Vlahos; Louis B Irving; Bruce D Levy; Gary P Anderson; Steven Bozinovski
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  188     ISSN:  1535-4970     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-07-16     Completed Date:  2013-09-27     Revised Date:  2014-07-21    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  179-86     Citation Subset:  AIM; IM    
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MeSH Terms
Bronchoalveolar Lavage Fluid / chemistry
Cells, Cultured
Disease Models, Animal
Flow Cytometry
Immunity, Innate
Inflammation / immunology
Interleukin-17 / blood,  immunology*
Lung / cytology,  immunology*
Neutrophil Infiltration / physiology
Neutrophils / immunology*,  pathology
Pulmonary Disease, Chronic Obstructive / blood,  immunology*
Respiratory Mucosa / immunology
Serum Amyloid A Protein / analysis,  immunology*
T-Lymphocyte Subsets / immunology
Grant Support
Reg. No./Substance:
0/Interleukin-17; 0/Serum Amyloid A Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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