Document Detail


Excessive fibrin deposition in nasal polyps caused by fibrinolytic impairment through reduction of tissue plasminogen activator expression.
MedLine Citation:
PMID:  23155140     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: Nasal polyps (NPs) are characterized by intense edema or formation of pseudocysts filled with plasma proteins, mainly albumin. However, the mechanisms underlying NP retention of plasma proteins in their submucosa remain unclear.
OBJECTIVES: We hypothesized that formation of a fibrin mesh retains plasma proteins in NPs. We assessed the fibrin deposition and expression of the components of the fibrinolytic system in patients with chronic rhinosinusitis (CRS).
METHODS: We assessed fibrin deposition in nasal tissue from patients with CRS and control subjects by means of immunofluorescence. Fibrinolytic components, d-dimer, and plasminogen activators were measured using ELISA, real-time PCR, and immunohistochemistry. We also performed gene expression and protein quantification analysis in cultured airway epithelial cells.
MEASUREMENTS AND MAIN RESULTS: Immunofluorescence data showed profound fibrin deposition in NP compared with uncinate tissue (UT) from patients with CRS and control subjects. Levels of the cross-linked fibrin cleavage product protein, d-dimer, were significantly decreased in NP compared with UT from patients with CRS and control subjects, suggesting reduced fibrinolysis (P < 0.05). Expression levels of tissue plasminogen activator (t-PA) mRNA and protein were significantly decreased in NP compared with UT from patients with CRS and control subjects (P < 0.01). Immunohistochemistry demonstrated clear reduction of t-PA in NP, primarily in the epithelium and glands. Th2 cytokine-stimulated cultured airway epithelial cells showed down-regulation of t-PA, suggesting a potential Th2 mechanism in NP.
CONCLUSIONS: A Th2-mediated reduction of t-PA might lead to excessive fibrin deposition in the submucosa of NP, which might contribute to the tissue remodeling and pathogenesis of CRS with nasal polyps.
Authors:
Tetsuji Takabayashi; Atsushi Kato; Anju T Peters; Kathryn E Hulse; Lydia A Suh; Roderick Carter; James Norton; Leslie C Grammer; Seong H Cho; Bruce K Tan; Rakesh K Chandra; David B Conley; Robert C Kern; Shigeharu Fujieda; Robert P Schleimer
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-15
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  187     ISSN:  1535-4970     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-02     Completed Date:  2013-03-17     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  49-57     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Blood Proteins / metabolism
Down-Regulation / physiology
Edema / metabolism
Epithelium / metabolism
Female
Fibrin / metabolism*
Fibrinolysis / physiology*
Fluorescent Antibody Technique
Humans
Male
Middle Aged
Nasal Mucosa / metabolism
Nasal Polyps / metabolism*
Th2 Cells / metabolism
Tissue Plasminogen Activator / metabolism*
Young Adult
Grant Support
ID/Acronym/Agency:
R01 HL078860/HL/NHLBI NIH HHS; R01AI072570/AI/NIAID NIH HHS; R01HL078860/HL/NHLBI NIH HHS; R37 HL068546/HL/NHLBI NIH HHS; R37HL068546-27/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Blood Proteins; 9001-31-4/Fibrin; EC 3.4.21.68/Tissue Plasminogen Activator
Comments/Corrections

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