RGD Reference Report - Role of the Fas/FasL system in a model of RSV infection in mechanically ventilated mice. - Rat Genome Database

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Role of the Fas/FasL system in a model of RSV infection in mechanically ventilated mice.

Authors: Van den Berg, E  Van Woensel, JB  Bos, AP  Bem, RA  Altemeier, WA  Gill, SE  Martin, TR  Matute-Bello, G 
Citation: van den Berg E, etal., Am J Physiol Lung Cell Mol Physiol. 2011 Jul 8.
RGD ID: 5135060
Pubmed: PMID:21743025   (View Abstract at PubMed)
PMCID: PMC3191752   (View Article at PubMed Central)
DOI: DOI:10.1152/ajplung.00368.2010   (Journal Full-text)

Infection with respiratory syncytial virus (RSV) in children can progress to respiratory distress and acute lung injury (ALI) necessitating mechanical ventilation (MV). MV enhances apoptosis and inflammation in mice infected with pneumonia virus of mice (PVM), a mouse pneumovirus that has been used as a model for severe RSV infection in mice. We hypothesized that the Fas/Fas ligand (FasL) system, a dual pro-apoptotic/pro-inflammatory system involved in other forms of lung injury, is required for enhanced lung injury in mechanically-ventilated mice infected with PVM. C57BL/6 mice and Fas-deficient ("lpr") mice were inoculated intratracheally with PVM. Seven or eight days after PVM inoculation the mice were subjected to 4 hours of MV (Tv 10 mL/kg, FiO(2) = 0.21 and PEEP = 3 cm H(2)O). Seven days after PVM inoculation, exposure to MV resulted in less severe injury in lpr mice than in C57BL/6 mice, as evidenced by decreased numbers of PMN in the BAL, and lower concentrations of the pro-inflammatory chemokines KC, MIP-1alpha and MIP-2 in the lungs. However, when PVM infection was allowed to progress one additional day, all of the lpr mice (7/7) died unexpectedly between one and 3.5 hours after the onset of ventilation, as compared with 3 of the 7 ventilated C57BL/6 mice. Parameters of lung injury were similar in non-ventilated mice, as was the viral content in the lungs and other organs. Thus, the Fas/FasL system was partly required for the lung inflammatory response in ventilated mice infected with PVM, but attenuation of lung inflammation did not prevent subsequent mortality.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
lung disease  ISOCxcl1 (Mus musculus)5135060; 5135060associated with Pneumonia more ...RGD 
lung disease  ISOCxcl2 (Mus musculus)5135060; 5135060associated with Pneumonia more ...RGD 
lung disease  IEP 5135060; 5135060associated with Pneumonia more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cxcl1  (C-X-C motif chemokine ligand 1)
Cxcl2  (C-X-C motif chemokine ligand 2)

Genes (Mus musculus)
Cxcl1  (C-X-C motif chemokine ligand 1)
Cxcl2  (C-X-C motif chemokine ligand 2)

Genes (Homo sapiens)
CXCL1  (C-X-C motif chemokine ligand 1)
CXCL2  (C-X-C motif chemokine ligand 2)


Additional Information