Linked Life Data

10235125

Source:http://linkedlifedata.com/resource/pubmed/id/10235125

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1999-5-26
pubmed:abstractText
The pathogenesis of Pneumocystis carinii pneumonia (PCP) suggests an important role for dysfunction of the pulmonary surfactant system in the hypoxemic respiratory insufficiency associated with this infection. Surfactant protein B (SP-B) is a hydrophobic protein shown to be essential for normal surfactant function in vivo. Therefore, we hypothesized that the inhibition of SP-B expression occurs during PCP, and we tested this hypothesis in two immunodeficient animal models. PCP was induced in C.B-17 scid/scid mice by intratracheal inoculation of P. carinii organisms. Infected lung homogenates, obtained at time points up to 6 weeks after inoculation, were analyzed for SP-B and mRNA content. When a comparison was made with uninfected scid controls, the densitometric quantitation of Western blots of lung homogenates demonstrated significant reductions in 8 kd SP-B in mice infected with P. carinii 4 weeks after inoculation (16% of the control value). Northern blot analysis showed a concomitant decrease in SP-B mRNA to 24% of the control level. The decrease in SP-B and mRNA levels in lung homogenates of infected mice was reflected in lower SP-B levels in the surfactant. An enzyme-linked immunosorbent assay for the SP-B level in surfactant prepared from bronchoalveolar lavage samples of infected scid mice demonstrated a significant reduction in alveolar SP-B content (45% of the control value). In contrast to the results with SP-B, neither the SP-A protein content nor the mRNA level was significantly altered by PCP infection. To confirm these observations, SP-B expression was studied in an additional animal model of PCP. The SP-B content of lung homogenates from BALB/c mice depleted of CD4+ T cells and infected with P. carinii was also reduced (51% of the control value). We conclude that P. carinii induces selective inhibition of the expression of SP-B in two mouse models of PCP and that this down-regulation is mediated at the level of mRNA expression. Therefore, an acquired deficiency of SP-B is likely to be an important contributor to the pathogenesis of hypoxemic respiratory failure that is observed in patients with PCP.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-2143
pubmed:author
pubmed:issnType
Print
pubmed:volume
133
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
423-33
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10235125-Animals, pubmed-meshheading:10235125-Bronchoalveolar Lavage Fluid, pubmed-meshheading:10235125-CD4-Positive T-Lymphocytes, pubmed-meshheading:10235125-Disease Models, Animal, pubmed-meshheading:10235125-Down-Regulation, pubmed-meshheading:10235125-Gene Expression Regulation, pubmed-meshheading:10235125-Humans, pubmed-meshheading:10235125-Lung, pubmed-meshheading:10235125-Mice, pubmed-meshheading:10235125-Mice, Inbred BALB C, pubmed-meshheading:10235125-Mice, SCID, pubmed-meshheading:10235125-Pneumonia, Pneumocystis, pubmed-meshheading:10235125-Proteolipids, pubmed-meshheading:10235125-Pulmonary Surfactant-Associated Protein A, pubmed-meshheading:10235125-Pulmonary Surfactant-Associated Proteins, pubmed-meshheading:10235125-Pulmonary Surfactants, pubmed-meshheading:10235125-RNA, Messenger, pubmed-meshheading:10235125-Respiratory Insufficiency
pubmed:year
1999
pubmed:articleTitle
Inhibition of lung surfactant protein B expression during Pneumocystis carinii pneumonia in mice.
pubmed:affiliation
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6068, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.