Kunath, Julia and Delaroque, Nicolas and Szardenings, Michael and Neundorf, Ines and Straub, Rainer H. (2017) Sympathetic nerve repulsion inhibited by designer molecules in vitro and role in experimental arthritis. LIFE SCIENCES, 168. pp. 47-53. ISSN 0024-3205, 1879-0631
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Aims: In rheumatoid arthritis and collagen type II arthritis (CIA), sympathetic nerve fibers get lost in inflamed tissue. The process is probably induced by nerve repellent factors like semaphorin 3F (SEMA3F). Repulsion of sympathetic nerve fibers in inflamed tissue has proinflammatory effects due to the loss of anti-inflammatory neurotransmitters. We hypothesized that design molecules like antibodies and specific peptides that inhibit nerve fiber repulsion can ameliorate CIA. Materials and methods: Two blocking antibodies were used and four blocking peptides were generated using the phage display technique with the targets of SEMA3F and plexin-A2. All blocking molecules were tested in vitro using a sympathetic neurite outgrowth assay. CIA was induced by collagen type II in mice. Key findings: In the neurite outgrowth assay, the two antibodies against plexin-A2 and neuropilin-2 as well as the four blocking peptides - two SEMA3F analogous peptides (WLFQRDPGDR, QATVKWLFQRDPGDRR) and two plexin A2 analogous peptides (DSSDQFSFDYELEQN, DSSIQFFSFEKDKERI) - were able to block sympathetic nerve fiber repulsion in vitro (at 150-600 nmol/1). Administration of the two antibodies prophylactically on day 4 after immunization did not change clinical CIA. Similarly, using the top candidate antibody to plexin-A2 after CIA onset (mild score of 4 points, maximum = 52 points), did not ameliorate CIA. The tested blocking peptides were not recovered in peripheral blood after i.v. and i.p. administration. Significance: While designer molecules blocked nerve fiber repulsion in vitro, therapeutic administration in vivo did not change CIA. Possible strategies to overcome negative effects demonstrated in vivo are discussed. (C) 2016 Elsevier Inc. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | COLLAGEN-INDUCED ARTHRITIS; REGULATORY T-CELLS; RHEUMATOID-ARTHRITIS; AXON GUIDANCE; GROWTH-FACTOR; LOW-DENSITY; RECEPTOR; FIBERS; SYSTEM; NEURONS; Sympathetic nerve fiber; Inflammation; Arthritis; Nerve fiber repulsion; Nerve repellent factors |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 12:58 |
| Last Modified: | 19 Feb 2019 07:17 |
| URI: | https://pred.uni-regensburg.de/id/eprint/127 |
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