RGD Reference Report - Immune reconstitution during Pneumocystis lung infection: disruption of surfactant component expression and function by S-nitrosylation. - Rat Genome Database

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Immune reconstitution during Pneumocystis lung infection: disruption of surfactant component expression and function by S-nitrosylation.

Authors: Atochina-Vasserman, EN  Gow, AJ  Abramova, H  Guo, CJ  Tomer, Y  Preston, AM  Beck, JM  Beers, MF 
Citation: Atochina-Vasserman EN, etal., J Immunol. 2009 Feb 15;182(4):2277-87.
RGD ID: 4143286
Pubmed: PMID:19201882   (View Abstract at PubMed)
PMCID: PMC4016818   (View Article at PubMed Central)
DOI: DOI:10.4049/jimmunol.0802775   (Journal Full-text)

Pneumocystis pneumonia (PCP), the most common opportunistic pulmonary infection associated with HIV infection, is marked by impaired gas exchange and significant hypoxemia. Immune reconstitution disease (IRD) represents a syndrome of paradoxical respiratory failure in patients with active or recently treated PCP subjected to immune reconstitution. To model IRD, C57BL/6 mice were selectively depleted of CD4(+) T cells using mAb GK1.5. Following inoculation with Pneumocystis murina cysts, infection was allowed to progress for 2 wk, GK1.5 was withdrawn, and mice were followed for another 2 or 4 wk. Flow cytometry of spleen cells demonstrated recovery of CD4(+) cells to >65% of nondepleted controls. Lung tissue and bronchoalveolar lavage fluid harvested from IRD mice were analyzed in tandem with samples from CD4-depleted mice that manifested progressive PCP for 6 wks. Despite significantly decreased pathogen burdens, IRD mice had persistent parenchymal lung inflammation, increased bronchoalveolar lavage fluid cellularity, markedly impaired surfactant biophysical function, and decreased amounts of surfactant phospholipid and surfactant protein (SP)-B. Paradoxically, IRD mice also had substantial increases in the lung collectin SP-D, including significant amounts of an S-nitrosylated form. By native PAGE, formation of S-nitrosylated SP-D in vivo resulted in disruption of SP-D multimers. Bronchoalveolar lavage fluid from IRD mice selectively enhanced macrophage chemotaxis in vitro, an effect that was blocked by ascorbate treatment. We conclude that while PCP impairs pulmonary function and produces abnormalities in surfactant components and biophysics, these responses are exacerbated by IRD. This worsening of pulmonary inflammation, in response to persistent Pneumocystis Ags, is mediated by recruitment of effector cells modulated by S-nitrosylated SP-D.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
immune system disease  ISOSftpb (Mus musculus)4143286; 4143286associated with Pneumonia more ...RGD 
immune system disease  ISOSftpd (Mus musculus)4143286; 4143286associated with Pneumonia more ...RGD 
immune system disease  IEP 4143286associated with Pneumonia more ...RGD 
immune system disease  IEP 4143286associated with Pneumonia more ...RGD 

Objects Annotated

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

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

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


Additional Information