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Targeted blockade in lethal West Nile virus encephalitis indicates a crucial role for very late antigen (VLA)-4-dependent recruitment of nitric oxide-producing macrophages
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نویسنده
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getts d.r. ,terry r.l. ,getts m.t. ,müller m. ,rana s. ,deffrasnes c. ,ashhurst t.m. ,radford j. ,hofer m. ,thomas s. ,campbell i.l. ,king n.j.c.
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منبع
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journal of neuroinflammation - 2012 - دوره : 9 - شماره : 0
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چکیده
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Infiltration of ly6chi monocytes from the blood is a hallmark of viral encephalitis. in mice with lethal encephalitis caused by west nile virus (wnv),an emerging neurotropic flavivirus,inhibition of ly6chi monocyte trafficking into the brain by anti-very late antigen (vla)-4 integrin antibody blockade at the time of first weight loss and leukocyte influx resulted in long-term survival of up to 60% of infected mice,with subsequent sterilizing immunity. this treatment had no effect on viral titers but appeared to be due to inhibition of ly6chi macrophage immigration. although macrophages isolated from the infected brain induced wnv-specific cd4+ t-cell proliferation,t cells did not directly contribute to pathology,but are likely to be important in viral control,as antibody-mediated t-cell depletion could not reproduce the therapeutic benefit of anti-vla-4. instead,70% of infiltrating inflammatory monocyte-derived macrophages were found to be making nitric oxide (no). furthermore,aminoguanidine-mediated inhibition of induced no synthase activity in infiltrating macrophages significantly prolonged survival,indicating involvement of no in the immunopathology. these data show for the first time the therapeutic effects of temporally targeting pathogenic no-producing macrophages during neurotropic viral encephalitis. © 2012 getts et al.; licensee biomed central ltd.
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کلیدواژه
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Flavivirus; Inflammatory monocytes; Integrins; Macrophage infiltration; Neurotropic virus; Nitric oxide; VLA-4; West Nile virus encephalitis
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آدرس
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the discipline of pathology,school of medical sciences faculty of medicine,the university of sydney,blackburn building d06,sydney,nsw 2006,australia,the bosch institute,university of sydney,sydney, Australia, the discipline of pathology,school of medical sciences faculty of medicine,the university of sydney,blackburn building d06,sydney,nsw 2006,australia,the bosch institute,university of sydney,sydney, Australia, the discipline of pathology,school of medical sciences faculty of medicine,the university of sydney,blackburn building d06,sydney,nsw 2006,australia,the bosch institute,university of sydney,sydney, Australia, the school of molecular biosciences,faculty of science,university of sydney,sydney,australia,the bosch institute,university of sydney,sydney, Australia, the discipline of pathology,school of medical sciences faculty of medicine,the university of sydney,blackburn building d06,sydney,nsw 2006,australia,the bosch institute,university of sydney,sydney, Australia, the discipline of pathology,school of medical sciences faculty of medicine,the university of sydney,blackburn building d06,sydney,nsw 2006,australia,the bosch institute,university of sydney,sydney, Australia, the discipline of pathology,school of medical sciences faculty of medicine,the university of sydney,blackburn building d06,sydney,nsw 2006,australia,the bosch institute,university of sydney,sydney, Australia, the discipline of pathology,school of medical sciences faculty of medicine,the university of sydney,blackburn building d06,sydney,nsw 2006,australia,the bosch institute,university of sydney,sydney, Australia, the school of molecular biosciences,faculty of science,university of sydney,sydney,australia,the bosch institute,university of sydney,sydney, Australia, the centre for vascular research,school of medical sciences,university of new south wales,sydney, Australia, the school of molecular biosciences,faculty of science,university of sydney,sydney,australia,the bosch institute,university of sydney,sydney, Australia, the discipline of pathology,school of medical sciences faculty of medicine,the university of sydney,blackburn building d06,sydney,nsw 2006,australia,the bosch institute,university of sydney,sydney, Australia
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Authors
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