Hypoxia increases macrophage motility, possibly by decreasing the heparan sulfate proteoglycan biosynthesis
| Autor: | Gunnel Östergren-Lundén, Göran Bondjers, Pia Stillemark-Billton, Germán Camejo, Annika Asplund |
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| Rok vydání: | 2009 |
| Předmět: |
Immunology
Down-Regulation Motility Biology chemistry.chemical_compound Biosynthesis Cell Movement medicine Humans Immunology and Allergy RNA Messenger Hypoxia Cell adhesion Transcription factor Cells Cultured chemistry.chemical_classification Messenger RNA Macrophages Cell Membrane Cell Biology Hypoxia (medical) Atherosclerosis Hypoxia-Inducible Factor 1 alpha Subunit Molecular biology carbohydrates (lipids) Cell Transformation Neoplastic Enzyme chemistry Tumor progression Syndecan-4 Syndecan-1 medicine.symptom Heparan Sulfate Proteoglycans |
| Zdroj: | Journal of Leukocyte Biology. 86:381-388 |
| ISSN: | 1938-3673 0741-5400 |
| DOI: | 10.1189/jlb.0908536 |
| Popis: | Hypoxia-induced modifications of HSPG may be of relevance for the development of atherosclerotic lesions and tumor progression. Macrophages are recruited and retained in hypoxic sites in atherosclerotic lesions and tumors. Furthermore, macrophages are suggested to be a major source of HSPG synthesis in atherosclerotic lesions. HSPG are, among other things, known to regulate cell motility, cell adhesion, and receptor interaction. The aim of this study was to investigate the effect of hypoxia on HSPG expression and macrophage motility. We also explored the potential regulation of HSPG by the transcription factor HIF-1α. The nondirected cell motility was increased in HMDM after 24 h exposure to hypoxia (0.5% O2) compared with normal cell culture condition (21% O2). Enzymatic degradation of HS GAG further increased the motility of the HMDM in hypoxia, indicating a role of reduced cell-associated HSPG in the increased HMDM motility. HMDM exposed to 24 h of hypoxia had lower mRNA expressions of syndecan-1 and −4 compared with cells exposed to normal cell culture conditions. Protein levels of syndecan-1 were also decreased significantly in response to hypoxia, and cells subjected to hypoxia had lower mRNA expression for key enzymes involved in HS biosynthesis. In addition, hypoxia was found to reduce the relative content of HS GAG. Transfecting THP-1 cells with siHIF-1α indicated that this transcription factor was not involved in the hypoxia-induced modifications of HSPG expression. Given the documented multiple functions of HSPG in macrophage behavior, the hypoxia-induced modifications of HSPG may be of relevance for the development of atherosclerotic lesions and tumor progression. |
| Databáze: | OpenAIRE |
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