Difference in proangiogenic potential of systemic and pulmonary endothelium: role of CXCR2

American Journal of Physiology - Lung Cellular and Molecular Physiology - Tập 288 Số 6 - Trang L1117-L1123 - 2005
Aigul Moldobaeva1, Elizabeth M. Wagner2
1Department of Medicine, Johns Hopkins University, Baltimore, Md., USA.
2Department of Medicine, Johns Hopkins University, Baltimore, Maryland

Tóm tắt

The systemic vasculature in and surrounding the lung is proangiogenic, whereas the pulmonary vasculature rarely participates in neovascularization. We studied the effects of the proangiogenic ELR+ CXC chemokine MIP-2 (macrophage inflammatory protein-2) on endothelial cell proliferation and chemotaxis. Mouse aortic, pulmonary arterial, and lung microvascular endothelial cells were isolated and subcultured. Proliferation ([3H]thymidine uptake) and migration (Transwell chemotaxis) were evaluated in each cell type at baseline and upon exposure to MIP-2 (1–100 ng/ml) without and with exposure to hypoxia (24 h)-reoxygenation. Baseline proliferation did not vary among cell types, and all cells showed increased proliferation after MIP-2. Aortic cell chemotaxis increased markedly upon exposure to MIP-2; however, neither pulmonary artery nor lung microvascular endothelial cells responded to this chemokine. Assessment of CXCR2, the G protein-coupled receptor through which MIP-2 signals, displayed no baseline difference in mRNA, protein, or cell surface expression among cell types. Exposure to hypoxia increased expression of CXCR2of aortic endothelial cells only. Additionally, aortic cells, compared with pulmonary cells, showed significantly greater protein and activity of cathepsin S, a proteolytic enzyme important for cell motility. Thus the combined effects of increased cathepsin S activity, providing increased motility and enhanced CXCR2expression after hypoxia, both contribute to the proangiogenic phenotype of systemic arterial endothelial cells.

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American Journal of Physiology - Lung Cellular and Molecular Physiology

Tập 288 Số 6

L1117-L1123

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