Linked Life Data

19542465

Source:http://linkedlifedata.com/resource/pubmed/id/19542465

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-6-22
pubmed:abstractText
There is an abundance of antimicrobial peptides in cystic fibrosis (CF) lungs. Despite this, individuals with CF are susceptible to microbial colonization and infection. In this study, we investigated the antimicrobial response within the CF lung, focusing on the human cathelicidin LL-37. We demonstrate the presence of the LL-37 precursor, human cathelicidin precursor protein designated 18-kDa cationic antimicrobial protein, in the CF lung along with evidence that it is processed to active LL-37 by proteinase-3. We demonstrate that despite supranormal levels of LL-37, the lung fluid from CF patients exhibits no demonstrable antimicrobial activity. Furthermore Pseudomonas killing by physiological concentrations of exogenous LL-37 is inhibited by CF bronchoalveolar lavage (BAL) fluid due to proteolytic degradation of LL-37 by neutrophil elastase and cathepsin D. The endogenous LL-37 in CF BAL fluid is protected from this proteolysis by interactions with glycosaminoglycans, but while this protects LL-37 from proteolysis it results in inactivation of LL-37 antimicrobial activity. By digesting glycosaminoglycans in CF BAL fluid, endogenous LL-37 is liberated and the antimicrobial properties of CF BAL fluid restored. High sodium concentrations also liberate LL-37 in CF BAL fluid in vitro. This is also seen in vivo in CF sputum where LL-37 is complexed to glycosaminoglycans but is liberated following nebulized hypertonic saline resulting in increased antimicrobial effect. These data suggest glycosaminoglycan-LL-37 complexes to be potential therapeutic targets. Factors that disrupt glycosaminoglycan-LL-37 aggregates promote the antimicrobial effects of LL-37 with the caveat that concomitant administration of antiproteases may be needed to protect the now liberated LL-37 from proteolytic cleavage.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
183
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
543-51
pubmed:meshHeading
pubmed-meshheading:19542465-Adjuvants, Immunologic, pubmed-meshheading:19542465-Adolescent, pubmed-meshheading:19542465-Antibody Specificity, pubmed-meshheading:19542465-Antimicrobial Cationic Peptides, pubmed-meshheading:19542465-Cathepsin D, pubmed-meshheading:19542465-Child, pubmed-meshheading:19542465-Cystic Fibrosis, pubmed-meshheading:19542465-Glycosaminoglycans, pubmed-meshheading:19542465-Humans, pubmed-meshheading:19542465-Hydrolysis, pubmed-meshheading:19542465-Leukocyte Elastase, pubmed-meshheading:19542465-Lung, pubmed-meshheading:19542465-Macromolecular Substances, pubmed-meshheading:19542465-Molecular Weight, pubmed-meshheading:19542465-Myeloblastin, pubmed-meshheading:19542465-Nebulizers and Vaporizers, pubmed-meshheading:19542465-Protein Precursors, pubmed-meshheading:19542465-Protein Processing, Post-Translational, pubmed-meshheading:19542465-Saline Solution, Hypertonic, pubmed-meshheading:19542465-Solubility, pubmed-meshheading:19542465-Sputum
pubmed:year
2009
pubmed:articleTitle
LL-37 complexation with glycosaminoglycans in cystic fibrosis lungs inhibits antimicrobial activity, which can be restored by hypertonic saline.
pubmed:affiliation
Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland. bergsson@here.is
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't