RGD Reference Report - Aspergillus fumigatus-induced allergic airway inflammation alters surfactant homeostasis and lung function in BALB/c mice. - Rat Genome Database

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Aspergillus fumigatus-induced allergic airway inflammation alters surfactant homeostasis and lung function in BALB/c mice.

Authors: Haczku, A  Atochina, EN  Tomer, Y  Chen, H  Scanlon, ST  Russo, S  Xu, J  Panettieri RA, JR  Beers, MF 
Citation: Haczku A, etal., Am J Respir Cell Mol Biol. 2001 Jul;25(1):45-50.
RGD ID: 4143465
Pubmed: PMID:11472974   (View Abstract at PubMed)
DOI: DOI:10.1165/ajrcmb.25.1.4391   (Journal Full-text)

The differential regulation of pulmonary surfactant proteins (SPs) is demonstrated in a murine model of Aspergillus fumigatus (Af )-induced allergic airway inflammation and hyperresponsiveness. BALB/c mice were sensitized intraperitoneally and challenged intranasally with Af extract. Enzyme-linked immunosorbent assay analysis of serum immunoglobulin (Ig) levels in these mice showed markedly increased total IgE and Af-specific IgE and IgG1. This was associated with peribronchial/perivascular tissue inflammation, airway eosinophilia, and secretion of interleukin (IL)-4 and IL-5 into the bronchoalveolar lavage fluid (BALF). Functional analysis revealed that in comparison with nonsensitized mice, allergic sensitization and challenge resulted in significant increases in acetylcholine responsiveness. To analyze levels of SPs, the cell-free supernate of the BALF was further fractionated by high-speed (20,000 x g) centrifugation. After sensitization and challenges, the pellet (large-aggregate fraction) showed a selective downregulation of hydrophobic SPs SP-B and SP-C by 50%. This reduction was reflected by commensurate decreases in SP-B and SP-C messenger RNA (mRNA) expression of the lung tissue of these animals. In contrast, there was a 9-fold increase in SP-D protein levels in the 20,000 x g supernate without changes in SP-D mRNA. The increased levels of SP-D showed a significant positive correlation with serum IgE (r = 0.85, P < 0.001). Tissue mRNA and protein levels of SP-A in either the large- or the small-aggregate fractions were unaffected. Our data indicate that allergic airway inflammation induces selective inhibition of hydrophobic SP synthesis accompanied by marked increases in the lung collectin SP-D protein content of BALF. These changes may contribute significantly to the pathophysiology of Af-induced allergic airway hyperresponsiveness.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
asthma  ISOSftpb (Mus musculus)4143465; 4143465mRNA and protein:decreased expression:lungRGD 
asthma  ISOSftpc (Mus musculus)4143465; 4143465mRNA and protein:decreased expression:lungRGD 
asthma  ISOSftpd (Mus musculus)4143465; 4143465protein:increased expression:lungRGD 
asthma  IEP 4143465; 4143465mRNA and protein:decreased expression:lungRGD 
asthma  IEP 4143465protein:increased expression:lungRGD 

Objects Annotated

Genes (Rattus norvegicus)
Sftpb  (surfactant protein B)
Sftpc  (surfactant protein C)
Sftpd  (surfactant protein D)

Genes (Mus musculus)
Sftpb  (surfactant associated protein B)
Sftpc  (surfactant associated protein C)
Sftpd  (surfactant associated protein D)

Genes (Homo sapiens)
SFTPB  (surfactant protein B)
SFTPC  (surfactant protein C)
SFTPD  (surfactant protein D)


Additional Information