title: Tumor necrosis factor-alpha-converting enzyme is expressed in the inflamed peripheral nervous system.
abstract: Tumor necrosis factor-alpha (TNF-alpha) is considered to play a critical role in the pathogenesis of immune-mediated inflammatory demyelinating disorders of the peripheral nervous system (PNS). Processing of membrane-bound inactive pro-TNF-alpha into the active soluble cytokine is mediated by a sheddase, the so-called TNF-alpha-converting enzyme (TACE), a member of the A Disintegrin and Metalloproteinase (ADAM) family. We explored the expression of TACE (ADAM-17) in sciatic nerves from Lewis rats with experimental autoimmune neuritis (EAN), an animal model of the Guillain-Barré syndrome (GBS), an immune-mediated polyradiculoneuropathy. To extend our study to human disease, sural nerve biopsies from GBS patients were investigated by immunohistochemistry. In EAN, T lymphocytes could be defined as the cellular source of ADAM-17 with peak expression levels at maximum clinical disease severity. Similarly, in human sural nerves, ADAM-17-expressing T cells could be localized primarily within the epi- and perineurium, whereas in control sections from patients with non-inflammatory neuropathies, no expression could be depicted. Our findings indicate that ADAM-17 is upregulated during EAN and expressed in nerves of GBS patients and thus may contribute to the pathogenesis of inflammatory demyelination of the PNS.
authors.affiliation: Department of Neurology, Research Group for Clinical and Experimental Neuroimmunology, Heinrich-Heine-University, Duesseldorf, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Kurz
authors.forename: Heidrun
authors.initials: H
authors.lastname: Pischel
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.forename: Bernd C
authors.initials: BC
authors.lastname: Kieseier
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000072198:ADAM17 Protein; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D004195:Disease Models, Animal; D053331:Ectodysplasins; D005260:Female; D005620:Freund's Adjuvant; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D020275:Guillain-Barre Syndrome / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008565:Membrane Proteins / Q000378:metabolism; D009444:Neuritis, Autoimmune, Experimental / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D020426:Sciatic Neuropathy / Q000209:etiology / Q000378:metabolism; D013497:Sural Nerve / Q000378:metabolism; D013997:Time Factors; D048069:Tumor Necrosis Factors / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C506018:EDA protein, human; D053331:Ectodysplasins; D008565:Membrane Proteins; D048069:Tumor Necrosis Factors; D005620:Freund's Adjuvant; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; C000606464:Adam17 protein, rat