Expression of matrix metalloproteinases in vasculitic neuropathy.
The aim of this study was to investigate the expression pattern and cellular source of matrix metalloproteinases (MMP) in vasculitic neuropathy. Matrix metalloproteinases are endopeptidases degrading components of extracellular matrix proteins, and they have been implicated in the pathogenesis of inflammatory demyelination. They are induced by cytokines, secreted by inflammatory cells, and enhance T cell migration. Vasculitic neuropathy occurs as a component of systemic vasculitis or as an isolated angiitis of the peripheral nervous system, and T cell-mediated inflammation is detected in its pathogenesis. Nerve biopsy sections of eight patients with nonsystemic vasculitic neuropathy (NSVN) and four with systemic vasculitic neuropathy were examined for the presence of CD4+, CD8+, and CD68+ cells and immunohistochemically for MMP-2 and MMP-9 expression. Nerve biopsies of eight patients with noninflammatory neuropathy were used as a control group. Semiquantitative polymerase chain reaction analysis was performed to detect MMP-2 and MMP-9 mRNA. The predominant cells were CD8+ and CD68+ T cells. Expression of MMP-9, but not MMP-2, was increased in perivascular inflammatory infiltrate in nerve tissues of vasculitic neuropathy patients. This MMP-9 expression correlated positively with immunostaining of CD8+ T cells. No difference was detected between immunostaining patterns of nonsystemic and systemic vasculitic neuropathies with the antibodies used, except in MMP-9 immunostaining, which was found to be enhanced in NSVN group. Polymerase chain reaction analysis revealed elevated mRNA levels of MMP-9 and MMP-2 compared with controls, but this did not reach statistical significance. Our results imply a pathogenic role for MMP-9 secreted from CD8+ cells in vasculitic neuropathy.
Gurer
Gunfer
G
Department of Neurology and Neuromuscular Diseases Research Laboratory, Hacettepe University Hospitals, 06100, Sihhiye, Ankara, Turkey. gunfergurer@yahoo.com
Erdem
Sevim
S
Kocaefe
Cetin
C
Ozgüç
Meral
M
Tan
Ersin
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D001706:Biopsy; D001808:Blood Vessels / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003711:Demyelinating Diseases / Q000201:enzymology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000201:enzymology* / Q000276:immunology / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D013497:Sural Nerve / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D014657:Vasculitis / Q000201:enzymology* / Q000276:immunology / Q000503:physiopathology; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020782:Matrix Metalloproteinases; D012333:RNA, Messenger; C067980:CD68 antigen, human; D000097382:CD68 Molecule