Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-2-5
pubmed:abstractText
Individuals with alpha(1)-antitrypsin (alpha(1)-AT) deficiency are at risk for early-onset destructive lung disease as a result of insufficient lower respiratory tract alpha(1)-AT and an increased burden of neutrophil products such as elastase. Human neutrophil peptides (HNP), the most abundant protein component of neutrophil azurophilic granules, represent another potential inflammatory component in lung disease characterized by increased numbers of activated or deteriorating neutrophils. The purpose of this study was to determine the role of HNP in lower respiratory tract inflammation and destruction occuring in alpha(1)-AT deficiency. alpha(1)-AT-deficient individuals (n = 33) and healthy control subjects (n = 21) were evaluated by bronchoalveolar lavage. HNP concentrations were significantly higher in alpha(1)-AT-deficient individuals (1,976 +/- 692 vs. 29 +/- 12 nM, P < 0.0001), and levels correlated with markers of neutrophil-mediated lung inflammation. In vitro, HNP produced a dose-dependent cytotoxic effect on alveolar macrophages and stimulated production of the potent neutrophil chemoattractants leukotriene B(4) and interleukin-8 by alveolar macrophages, with a 6- to 10-fold increase in chemoattractant production over negative control cultures (P < 0.05). A synergistic effect was noted between HNP and neutrophil elastase with regard to leukotriene B(4) production. Importantly, the proinflammatory effects of HNP were blocked by alpha(1)-AT. HNP likely play an important role in amplifying and maintaining neutrophil-mediated inflammation in the lungs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1040-0605
pubmed:author
pubmed:issnType
Print
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
L514-20
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:14594730-Adult, pubmed-meshheading:14594730-Bronchoalveolar Lavage Fluid, pubmed-meshheading:14594730-Cells, Cultured, pubmed-meshheading:14594730-Cytotoxicity Tests, Immunologic, pubmed-meshheading:14594730-Dose-Response Relationship, Immunologic, pubmed-meshheading:14594730-Female, pubmed-meshheading:14594730-Humans, pubmed-meshheading:14594730-Interleukin-8, pubmed-meshheading:14594730-Leukocyte Elastase, pubmed-meshheading:14594730-Leukotriene B4, pubmed-meshheading:14594730-Macrophages, Alveolar, pubmed-meshheading:14594730-Male, pubmed-meshheading:14594730-Middle Aged, pubmed-meshheading:14594730-Neutrophils, pubmed-meshheading:14594730-Pneumonia, pubmed-meshheading:14594730-alpha 1-Antitrypsin, pubmed-meshheading:14594730-alpha 1-Antitrypsin Deficiency, pubmed-meshheading:14594730-alpha-Defensins
pubmed:year
2004
pubmed:articleTitle
Role of human neutrophil peptides in lung inflammation associated with alpha1-antitrypsin deficiency.
pubmed:affiliation
Division of Pulmonary Diseases, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32610-0296, USA. spenclt@peds.ufl.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.