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EMAP II Overexpression Induces Endothelial Apoptosis and Emphysema in Murine Lungs
Author(s) -
Clauss Matthias,
Rajashekhar Gangaraju,
Sigua Ninotchka,
Kamocki Krzysztof,
Ahlbrecht Katrin,
Yildirim Ali Oender,
Fehrenbach Heinz,
Voswinckel Robert,
Petrache Irina
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.47.8
Subject(s) - bronchoalveolar lavage , apoptosis , lung , pathology , parenchyma , genetically modified mouse , immunohistochemistry , monocyte , biology , immunology , transgene , medicine , biochemistry , gene
Objective: Endothelial Monocyte‐Activating Polypeptide II (EMAP II) is a monocyte attracting, anti‐angiogenic and endothelial cells apoptosis inducing pro‐inflammatory cytokine. Based on our previous work linking endothelial apoptosis to emphysema we tested the hypothesis that inducible overexpression of EMAP II leads to apoptosis and emphysema in murine lungs. Methods: A transgenic murine model of tetracycline‐inducible lung specific EMAP II expression was employed. EMAP II overexpression was analyzed by Western immunoblotting of bronchoalveolar lavage fluid and immunohistochemistry of lung tissue. Endothelial apoptosis was determined in lung sections treated with active caspase‐3‐ and VE‐cadherin‐specific fluorescent‐labeled antibodies using confocal microscopy. Lung sections were stained with H&E for morphometric analysis of airspace enlargement. Results: Lung‐specific EMAP II overexpression resulted in a significant increase in caspase‐3 positive cells in lung parenchyma. A marked decrease in alveolar surface density was observed in transgenic mice after 3 months of induction compared to controls (39.4 + 2.4 vs 46.2 + 0.6 mm2/mm3, p=0.001). Conclusion: Transgenic EMAP II overexpression leads to increased endothelial apoptosis and emphysema‐like morphologic changes in murine lungs. These results suggest that EMAP II may contribute to the pathophysiology of emphysema development.