دورية أكاديمية
Macrophage activation associated with chronic murine cytomegalovirus infection results in more severe experimental choroidal neovascularization.
| العنوان: | Macrophage activation associated with chronic murine cytomegalovirus infection results in more severe experimental choroidal neovascularization. |
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| المؤلفون: | Scott W Cousins, Diego G Espinosa-Heidmann, Daniel M Miller, Simone Pereira-Simon, Eleut P Hernandez, Hsin Chien, Courtney Meier-Jewett, Richard D Dix |
| المصدر: | PLoS Pathogens, Vol 8, Iss 4, p e1002671 (2012) |
| بيانات النشر: | Public Library of Science (PLoS), 2012. |
| سنة النشر: | 2012 |
| المجموعة: | LCC:Immunologic diseases. Allergy LCC:Biology (General) |
| مصطلحات موضوعية: | Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5 |
| الوصف: | The neovascular (wet) form of age-related macular degeneration (AMD) leads to vision loss due to choroidal neovascularization (CNV). Since macrophages are important in CNV development, and cytomegalovirus (CMV)-specific IgG serum titers in patients with wet AMD are elevated, we hypothesized that chronic CMV infection contributes to wet AMD, possibly by pro-angiogenic macrophage activation. This hypothesis was tested using an established mouse model of experimental CNV. At 6 days, 6 weeks, or 12 weeks after infection with murine CMV (MCMV), laser-induced CNV was performed, and CNV severity was determined 4 weeks later by analysis of choroidal flatmounts. Although all MCMV-infected mice exhibited more severe CNV when compared with control mice, the most severe CNV developed in mice with chronic infection, a time when MCMV-specific gene sequences could not be detected within choroidal tissues. Splenic macrophages collected from mice with chronic MCMV infection, however, expressed significantly greater levels of TNF-α, COX-2, MMP-9, and, most significantly, VEGF transcripts by quantitative RT-PCR assay when compared to splenic macrophages from control mice. Direct MCMV infection of monolayers of IC-21 mouse macrophages confirmed significant stimulation of VEGF mRNA and VEGF protein as determined by quantitative RT-PCR assay, ELISA, and immunostaining. Stimulation of VEGF production in vivo and in vitro was sensitive to the antiviral ganciclovir. These studies suggest that chronic CMV infection may serve as a heretofore unrecognized risk factor in the pathogenesis of wet AMD. One mechanism by which chronic CMV infection might promote increased CNV severity is via stimulation of macrophages to make pro-angiogenic factors (VEGF), an outcome that requires active virus replication. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1553-7366 1553-7374 |
| العلاقة: | http://europepmc.org/articles/PMC3343109?pdf=renderTest; https://doaj.org/toc/1553-7366Test; https://doaj.org/toc/1553-7374Test |
| DOI: | 10.1371/journal.ppat.1002671 |
| الوصول الحر: | https://doaj.org/article/26df695e603b4ba8b7fde47efe13b759Test |
| رقم الانضمام: | edsdoj.26df695e603b4ba8b7fde47efe13b759 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 15537366 15537374 |
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| DOI: | 10.1371/journal.ppat.1002671 |