Vascular endothelial growth factor enhances macrophage clearance of apoptotic cells

Efficient clearance of apoptotic cells from the lung by alveolar macrophages is important for the maintenance of tissue structure and function. Lung tissue from humans with emphysema contains increased numbers of apoptotic cells and decreased levels of vascular endothelial growth factor (VEGF). Mice...

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Bibliographic Details
Published in:American journal of physiology. Lung cellular and molecular physiology 2012-04, Vol.302 (7), p.L711-L718
Main Authors: Kearns, Mark T, Dalal, Samay, Horstmann, Sarah A, Richens, Tiffany R, Tanaka, Takeshi, Doe, Jenna M, Boe, Darren M, Voelkel, Norbert F, Taraseviciene-Stewart, Laimute, Janssen, William J, Lee, Chun G, Elias, Jack A, Bratton, Donna, Tuder, Rubin M, Henson, Peter M, Vandivier, R William
Format: Article
Language:English
Subjects:
Alveoli
Animals
Antibodies
Antibodies, Monoclonal
Apoptosis
Cell Line
Cells
Data processing
Doxycycline - administration & dosage
Doxycycline - pharmacology
Emphysema
Emphysema - immunology
Emphysema - metabolism
Humans
Indoles - administration & dosage
Indoles - pharmacology
Jurkat Cells
Lung
Lung - cytology
Lung - metabolism
Lungs
Macrophages
Macrophages, Alveolar - immunology
Macrophages, Alveolar - physiology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Monocytes
Pyrroles - administration & dosage
Pyrroles - pharmacology
rac1 GTP-Binding Protein - metabolism
Rac1 protein
Rodents
Structure-function relationships
Tissues
Vascular endothelial growth factor
Vascular Endothelial Growth Factor A - antagonists & inhibitors
Vascular Endothelial Growth Factor A - metabolism
Vascular Endothelial Growth Factor Receptor-1 - immunology
Vascular Endothelial Growth Factor Receptor-1 - metabolism
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Summary:Efficient clearance of apoptotic cells from the lung by alveolar macrophages is important for the maintenance of tissue structure and function. Lung tissue from humans with emphysema contains increased numbers of apoptotic cells and decreased levels of vascular endothelial growth factor (VEGF). Mice treated with VEGF receptor inhibitors have increased numbers of apoptotic cells and develop emphysema. We hypothesized that VEGF regulates apoptotic cell clearance by alveolar macrophages (AM) via its interaction with VEGF receptor 1 (VEGF R1). Our data show that the uptake of apoptotic cells by murine AMs and human monocyte-derived macrophages is inhibited by depletion of VEGF and that VEGF activates Rac1. Antibody blockade or pharmacological inhibition of VEGF R1 activity also decreased apoptotic cell uptake ex vivo. Conversely, overexpression of VEGF significantly enhanced apoptotic cell uptake by AMs in vivo. These results indicate that VEGF serves a positive regulatory role via its interaction with VEGF R1 to activate Rac1 and enhance AM apoptotic cell clearance.
ISSN:1040-0605
1522-1504
DOI:10.1152/ajplung.00116.2011