Document Detail


Cystic fibrosis: a mucosal immunodeficiency syndrome.
MedLine Citation:
PMID:  22481418     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cystic fibrosis transmembrane conductance regulator (CFTR) functions as a channel that regulates the transport of ions and the movement of water across the epithelial barrier. Mutations in CFTR, which form the basis for the clinical manifestations of cystic fibrosis, affect the epithelial innate immune function in the lung, resulting in exaggerated and ineffective airway inflammation that fails to eradicate pulmonary pathogens. Compounding the effects of excessive neutrophil recruitment, the mutant CFTR channel does not transport antioxidants to counteract neutrophil-associated oxidative stress. Whereas mutant CFTR expression in leukocytes outside of the lung does not markedly impair their function, the expected regulation of inflammation in the airways is clearly deficient in cystic fibrosis. The resulting bacterial infections, which are caused by organisms that have substantial genetic and metabolic flexibility, can resist multiple classes of antibiotics and evade phagocytic clearance. The development of animal models that approximate the human pulmonary phenotypes-airway inflammation and spontaneous infection-may provide the much-needed tools to establish how CFTR regulates mucosal immunity and to test directly the effect of pharmacologic potentiation and correction of mutant CFTR function on bacterial clearance.
Authors:
Taylor Sitarik Cohen; Alice Prince
Related Documents :
6259718 - The phagocytic system in host defense.
21952678 - Evidence of conserved neuroendocrine interactions in the thymus: intrathymic expression...
19995678 - The immune effects of naturally occurring and synthetic nanoparticles.
16428838 - Activation of murine peritoneal macrophages by water-soluble extracts of bursaphelenchu...
19322708 - Functions exerted by the virulence-associated type-three secretion systems during salmo...
9388128 - Effects of lovastatin on the immune system.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review     Date:  2012-04-05
Journal Detail:
Title:  Nature medicine     Volume:  18     ISSN:  1546-170X     ISO Abbreviation:  Nat. Med.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-06     Completed Date:  2012-06-07     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  9502015     Medline TA:  Nat Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  509-19     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, Columbia University, New York, New York, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Cystic Fibrosis / etiology,  genetics*
Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
Humans
Immunologic Deficiency Syndromes / genetics*
Inflammation / etiology,  virology
Mucous Membrane / immunology
Mutation / genetics*
Phenotype
Respiratory System / physiopathology
Grant Support
ID/Acronym/Agency:
2R01HL079395/HL/NHLBI NIH HHS; 5R01HL073989/HL/NHLBI NIH HHS; 5R21AI083491/AI/NIAID NIH HHS; R01 HL073989/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator
Comments/Corrections

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


Previous Document:  Straight talk with...David Kaslow.
Next Document:  Community-Based Treatment of Serious Bacterial Infections in Newborns and Young Infants: A Randomize...