RGD Reference Report - Granzyme A- and B-cluster deficiency delays acute lung injury in pneumovirus-infected mice. - Rat Genome Database

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Granzyme A- and B-cluster deficiency delays acute lung injury in pneumovirus-infected mice.

Authors: Bem, RA  Van Woensel, JB  Lutter, R  Domachowske, JB  Medema, JP  Rosenberg, HF  Bos, AP 
Citation: Bem RA, etal., J Immunol. 2010 Jan 15;184(2):931-8. Epub 2009 Dec 16.
RGD ID: 5135517
Pubmed: PMID:20018616   (View Abstract at PubMed)
PMCID: PMC2803336   (View Article at PubMed Central)
DOI: DOI:10.4049/jimmunol.0903029   (Journal Full-text)

Lower respiratory tract infection by the human pneumovirus respiratory syncytial virus is a frequent cause of acute lung injury in children. Severe pneumovirus disease in humans is associated with activation of the granzyme pathway by effector lymphocytes, which may promote pathology by exaggerating proapoptotic caspase activity and proinflammatory activity. The main goal of this study was to determine whether granzymes contribute to the development of acute lung injury in pneumovirus-infected mice. Granzyme-expressing mice and granzyme A- and B-cluster single- and double-knockout mice were inoculated with the rodent pneumovirus pneumonia virus of mice strain J3666, and were studied for markers of lung inflammation and injury. Expression of granzyme A and B is detected in effector lymphocytes in mouse lungs in response to pneumovirus infection. Mice deficient for granzyme A and the granzyme B cluster have unchanged virus titers in the lungs but show a significantly delayed clinical response to fatal pneumovirus infection, a feature that is associated with delayed neutrophil recruitment, diminished activation of caspase-3, and reduced lung permeability. We conclude that granzyme A- and B-cluster deficiency delays the acute progression of pneumovirus disease by reducing alveolar injury.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Acute Lung Injury  ISOGzmb (Mus musculus)5135517; 5135517 RGD 
Acute Lung Injury  IEP 5135517 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gzmb  (granzyme B)

Genes (Mus musculus)
Gzmb  (granzyme B)

Genes (Homo sapiens)
GZMB  (granzyme B)


Additional Information