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

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 288; no. 6; pp. L1117 - L1123
• Main Authors: Moldobaeva, Aigul, Wagner, Elizabeth M
• Format: Journal Article
• Language: English
• Published: United States 01.06.2005
• Subjects: Animals; Aorta - immunology; Aorta - metabolism; Aorta - pathology; Cathepsins - metabolism; Cell Hypoxia; Cell Movement; Cell Proliferation; Chemokine CXCL2; Chemotactic Factors - metabolism; Chemotaxis; Endothelium, Vascular - cytology; Endothelium, Vascular - immunology; Endothelium, Vascular - metabolism; Lung - cytology; Lung - immunology; Lung - metabolism; Mice; Mice, Inbred C57BL; Microcirculation - cytology; Microcirculation - immunology; Microcirculation - metabolism; Monokines - metabolism; Neovascularization, Physiologic - physiology; Pulmonary Artery - cytology; Pulmonary Artery - immunology; Pulmonary Artery - metabolism; Receptors, Cell Surface; Receptors, Interleukin-8B - metabolism
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00370.2004

Department of Medicine, Johns Hopkins University, Baltimore, Maryland Submitted 4 October 2004 ; accepted in final form 11 February 2005 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 ([ 3 H]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 CXCR 2 , 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 CXCR 2 of 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 CXCR 2 expression after hypoxia, both contribute to the proangiogenic phenotype of systemic arterial endothelial cells. angiogenesis; cathepsin S; hypoxia-reoxygenation; macrophage inflammatory protein-2 Address for reprint requests and other correspondence: E. M. Wagner, Johns Hopkins Asthma and Allergy Center, Div. of Pulmonary and Critical Care Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224 (E-mail: wagnerem{at}jhmi.edu )