RGD Reference Report - Altered lymphocyte trafficking and diminished airway reactivity in transgenic mice expressing human MMP-9 in a mouse model of asthma. - Rat Genome Database

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Altered lymphocyte trafficking and diminished airway reactivity in transgenic mice expressing human MMP-9 in a mouse model of asthma.

Authors: Mehra, D  Sternberg, DI  Jia, Y  Canfield, S  Lemaitre, V  Nkyimbeng, T  Wilder, J  Sonett, J  D'Armiento, J 
Citation: Mehra D, etal., Am J Physiol Lung Cell Mol Physiol. 2010 Feb;298(2):L189-96. Epub 2009 Nov 25.
RGD ID: 5129522
Pubmed: PMID:19940022   (View Abstract at PubMed)
PMCID: PMC2822563   (View Article at PubMed Central)
DOI: DOI:10.1152/ajplung.00042.2009   (Journal Full-text)

Matrix metalloproteinase-9 (MMP-9) is hypothesized to facilitate leukocyte extravasation and extracellular remodeling in asthmatic airways. Careful descriptive studies have shown that MMP-9 levels are higher in the sputum of asthmatics; however, the consequence of increased MMP-9 activity has not been determined in this disease. We induced asthma in transgenic mice that express human MMP-9 in the murine lung tissue macrophage to determine the direct effect of human MMP-9 expression on airway inflammation. Transgenic (TG) and wild-type (WT) mice were immunized and challenged with ovalbumin. Forty-eight hours after the ovalbumin challenge, airway hyperresponsiveness (AHR) was measured, and inflammatory cell infiltration was evaluated in bronchoalveolar lavage fluid (BALF) and lung tissue. Baseline levels of inflammation were similar in the TG and WT groups of mice, and pulmonary eosinophilia was established in both groups by sensitization and challenge with ovalbumin. There was a significant reduction in AHR in sensitized and challenged trangenics compared with WT controls. Although total BALF cell counts were similar in both groups, the lymphocyte number in the lavage of the TG group was significantly diminished compared with the WT group (0.25 +/- 0.08 vs. 0.89 +/- 0.53; P = 0.0032). In addition, the draining lymphocytes were found to be larger in the TG animals compared with the WT mice. Equal numbers of macrophages, eosinophils, and neutrophils were seen in both groups. IL-13 levels were found to be lower in the sensitized TG compared with the WT mice. These results demonstrate an inverse relationship between human MMP-9 and AHR and suggest that MMP-9 expression alters leukocyte extravasation by reducing lymphocyte accumulation in the walls of asthmatic airways.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
asthma  IMP 5129522 RGD 
asthma  ISOMMP9 (Homo sapiens)5129522; 5129522 RGD 
Bronchial Hyperreactivity  IMP 5129522 RGD 
Bronchial Hyperreactivity  ISOMMP9 (Homo sapiens)5129522; 5129522 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mmp9  (matrix metallopeptidase 9)

Genes (Mus musculus)
Mmp9  (matrix metallopeptidase 9)

Genes (Homo sapiens)
MMP9  (matrix metallopeptidase 9)


Additional Information