Linked Life Data

16547274

Source:http://linkedlifedata.com/resource/pubmed/id/16547274

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2006-3-20
pubmed:abstractText
Pulmonary inflammation, abnormalities in alveolar type II cell and macrophage morphology, and pulmonary fibrosis are features of Hermansky-Pudlak Syndrome (HPS). We used the naturally occurring "pearl" HPS2 mouse model to investigate the mechanisms of lung inflammation observed in HPS. Although baseline bronchoalveolar lavage (BAL) cell counts and differentials were similar in pearl and strain-matched wild-type (WT) mice, elevated levels of proinflammatory (MIP1gamma) and counterregulatory (IL-12p40, soluble TNFr1/2) factors, but not TNF-alpha, were detected in BAL from pearl mice. After intranasal LPS challenge, BAL levels of TNF-alpha, MIP1alpha, KC, and MCP-1 were 2- to 3-fold greater in pearl than WT mice. At baseline, cultured pearl alveolar macrophages (AMs) had markedly increased production of inflammatory cytokines. Furthermore, pearl AMs had exaggerated TNF-alpha responses to TLR4, TLR2, and TLR3 ligands, as well as increased IFN-gamma/LPS-induced NO production. After 24 h in culture, pearl AM LPS responses reverted to WT levels, and pearl AMs were appropriately refractory to continuous LPS exposure. In contrast, cultured pearl peritoneal macrophages and peripheral blood monocytes did not produce TNF-alpha at baseline and had LPS responses which were no different from WT controls. Exposure of WT AMs to heat- and protease-labile components of pearl BAL, but not WT BAL, resulted in robust TNF-alpha secretion. Similar abnormalities were identified in AMs and BAL from another HPS model, pale ear HPS1 mice. We conclude that the lungs of HPS mice exhibit hyperresponsiveness to LPS and constitutive and organ-specific macrophage activation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
176
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4361-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16547274-Administration, Intranasal, pubmed-meshheading:16547274-Animals, pubmed-meshheading:16547274-Biological Markers, pubmed-meshheading:16547274-Cell Separation, pubmed-meshheading:16547274-Cells, Cultured, pubmed-meshheading:16547274-Cytokines, pubmed-meshheading:16547274-Disease Models, Animal, pubmed-meshheading:16547274-Endotoxins, pubmed-meshheading:16547274-Hermanski-Pudlak Syndrome, pubmed-meshheading:16547274-Hypersensitivity, pubmed-meshheading:16547274-Inflammation, pubmed-meshheading:16547274-Lipopolysaccharides, pubmed-meshheading:16547274-Lung, pubmed-meshheading:16547274-Macrophage Activation, pubmed-meshheading:16547274-Macrophages, Alveolar, pubmed-meshheading:16547274-Macrophages, Peritoneal, pubmed-meshheading:16547274-Mice, pubmed-meshheading:16547274-Nitric Oxide, pubmed-meshheading:16547274-Time Factors, pubmed-meshheading:16547274-Toll-Like Receptor 4
pubmed:year
2006
pubmed:articleTitle
Lung-restricted macrophage activation in the pearl mouse model of Hermansky-Pudlak syndrome.
pubmed:affiliation
Department of Medicine, Division of Pulmonary and Critical Care, University of Cincinnati, OH 45267, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural