Chronic inflammatory demyelinating polyneuropathy: decreased claudin-5 and relocated ZO-1
- Department of Neurology and Neurological Science, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan
- Correspondence to: Dr T Kanda Department of Neurology and Neurological Science, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan; t-kanda.nurotmd.ac.jp
- Received 11 August 2003
- Accepted 30 September 2003
- Revised 29 September 2003
Abstract
Objectives: To clarify the dynamics of molecules composing the blood–nerve barrier (BNB) in inflammatory neuropathies.
Methods: The expression of four tight junction (TJ) proteins—claudin-1, claudin-5, occludin, and ZO-1—was analysed immunohistochemically in sural nerve biopsy specimens obtained from patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).
Results: Claudin-1 was detected only in perineurial cells, whereas claudin-5 was present in endothelial cells, irrespective of vessel location or size. Occludin and ZO-1 were found in perineurial cells, in addition to some epineurial and endoneurial endothelial cells. In CIDP, percentages of endoneurial small vessels immunoreactive for claudin-5 were significantly decreased, as were ZO-1 immunoreactive endoneurial small vessels, with staining localised to interfaces between cells. Claudin-1 and occludin immunoreactivity did not differ appreciably between the neuropathies examined.
Conclusions: The downregulation of claudin-5 and altered localisation of ZO-1 seen in CIDP specimens may indicate that BNB derangement occurs in inflammatory neuropathies. Further investigation of TJ molecules may suggest new treatments based on properties of the BNB.
- claudin-1
- claudin-5
- occluding
- ZO-1
- chronic inflammatory demyelinating polyneuropathy
- blood–nerve barrier
- sural nerve
- BBB, blood–brain barrier
- BMEC, brain microvascular endothelial cell
- BNB, blood–nerve barrier
- CNS, central nervous system
- CIDP, chronic inflammatory demyelinating polyneuropathy
- PBS, phosphate buffered saline
- PNS, peripheral nervous system
- TJ, tight junction
- VEGF, vascular endothelial growth factor
Footnotes
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Competing interest: none declared
