期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 186, 期 7, 页码 1754-1761出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2016.03.007
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资金
- NIH/National Institute of Neurological Diseases and Stroke grants [R01 NS082116, R01 NS040237]
- NIH Nonhuman Primate Reagent Resource grants [RR016001, AI040101]
Traffic of activated monocytes into the dorsal root ganglia (DRG) is critical for pathology in HIV peripheral neuropathy. We have shown that accumulation of recently recruited (bromodeoxyuridine(+) MAC387(+)) monocytes is associated with severe DRG pathology and loss of intraepidermal nerve fibers in SIV-infected macaques. Herein, we blocked Leukocyte traffic by treating animals with natalizumab, which binds to alpha 4-integrins. SIV-infected CD8-depleted macaques treated with natalizumab either early (the day of infection) or Late (28 days after infection) were compared with untreated SIV-infected animals sacrificed at similar times. Histopathology showed diminished DRG pathology with natalizumab treatment, including decreased inflammation, neuronophagia, and Nageotte nodules. Natalizumab treatment resulted in a decrease in the number of bromodeoxyuridine(+) (early), MAC387(+) (late), CD68(+) (early and late), and SIVp28(+) (late) macrophages in DRG tissues. The number of CD3(+) T Lymphocytes in DRGs was not affected by natalizumab treatment. Vascular cell adhesion molecule 1, an adhesion molecule that mediates leukocyte traffic, was diminished in DRGs of all natalizumab-treated animals. These data show that blocking monocyte, but not T Lymphocyte, traffic to the DRG results in decreased inflammation and pathology, supporting a role for monocyte traffic and activation in HIV peripheral neuropathy.
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