Expression of Tie-2 by Human Monocytes and Their Responses to Angiopoietin-2.
From: Tumor Targeting Group, Academic Unit of Pathology, Division of Genomic Medicine, The Sir Henry Wellcome Laboratories for Medical Research, University of Sheffield Medical School, Sheffield, United Kingdom.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: Jun 2007
- ISSN: 0022-1767
- Volume: 178
- Issue: 11
- Pages: 7405-11
- Medium: Print
- Language: English
- Citation (JAMA): Murdoch Craig, Tazzyman Simon, Webster Steve, et al. Expression of Tie-2 by Human Monocytes and Their Responses to Angiopoietin-2.. J. Immunol. Jun 2007;178:7405-11
Abstract
Angiopoietins 1 and 2 bind to Tie-2 expressed on endothelial cells and regulate vessel stabilization and angiogenesis. Tie-2(+) monocytes have been shown to be recruited to experimental tumors where they promote tumor angiogenesis. In this study, we show that 20% of CD14(+) human blood monocytes express Tie-2, and that these cells coexpress CD16 (FcgammaRIII) and are predominantly CD34 negative. Ang-2 is up-regulated by endothelial cells in malignant tumors and inflamed tissues, so our finding that Ang-2 is a chemoattractant for human Tie-2(+) monocytes and macrophages, suggests that it may help to recruit and regulate their distribution in such tissues. Ang-2 was also found to markedly inhibit release of the important proinflammatory cytokine, TNF-alpha, by monocytes in vitro. Following extravasation of monocytes, and their differentiation into macrophages, many accumulate in the hypoxic areas of inflamed and malignant tissues. Ang-2 is known to be up-regulated by hypoxia and we show that monocytes and macrophages up-regulate Tie-2 when exposed to hypoxia. Furthermore, hypoxia augmented the inhibitory effect of Ang-2 on the release of the anti-angiogenic cytokine, IL-12 by monocytes. In sum, our data indicate that Ang-2 may recruit Tie-2(+) monocytes to tumors and sites of inflammation, modulate their release of important cytokines and stimulate them to express a proangiogenic phenotype.
Mesh Headings (Keywords): Angiopoietin-2, Animals, Cell Hypoxia, Cell Membrane, Cells, Cultured, Chemotaxis, Leukocyte, Cytokines, Gene Expression Regulation, Granulocytes, Humans, Inflammation Mediators, Lymphocyte Subsets, Macrophages, Mice, Monocytes, Neoplasms, Experimental, Neovascularization, Pathologic, RNA, Messenger, Receptor, TIE-2, Up-Regulation
Check for Full Text / PubMed Unique Identifier (PMID): 17513791
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