title: α4-Integrin Antibody Treatment Blocks Monocyte/Macrophage Traffic to, Vascular Cell Adhesion Molecule-1 Expression in, and Pathology of the Dorsal Root Ganglia in an SIV Macaque Model of HIV-Peripheral Neuropathy.
abstract: 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 α4-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.
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, Massachusetts.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Lakritz
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, Massachusetts.
authors.forename: Derek M
authors.initials: DM
authors.lastname: Thibault
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, Massachusetts.
authors.forename: Jake A
authors.initials: JA
authors.lastname: Robinson
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, Massachusetts.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Campbell
authors.affiliation: Section of Anatomic Pathology, Department of Biomedical Sciences, Cornell University College of Veterinary Medicine, Ithaca, New York.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Miller
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, Massachusetts.
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Williams
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, Massachusetts. Electronic address: burdot@bc.edu.
authors.forename: Tricia H
authors.initials: TH
authors.lastname: Burdo
mesh_terms: D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D005727:Ganglia, Spinal / Q000473:pathology*; D015658:HIV Infections; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000494:pharmacology; D039441:Integrin alpha4 / Q000378:metabolism*; D008253:Macaca mulatta; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D000069442:Natalizumab / Q000494:pharmacology; D010523:Peripheral Nervous System Diseases / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
chemical_list: D007155:Immunologic Factors; D000069442:Natalizumab; D019010:Vascular Cell Adhesion Molecule-1; D039441:Integrin alpha4