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Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 2004 May;75(5):765–769. doi: 10.1136/jnnp.2003.025692

Chronic inflammatory demyelinating polyneuropathy: decreased claudin-5 and relocated ZO-1

T Kanda 1, Y Numata 1, H Mizusawa 1
PMCID: PMC1763546  PMID: 15090575

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.

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Selected References

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  1. Bell M. A., Weddell A. G. A descriptive study of the blood vessels of the sciatic nerve in the rat, man and other mammals. Brain. 1984 Sep;107(Pt 3):871–898. doi: 10.1093/brain/107.3.871. [DOI] [PubMed] [Google Scholar]
  2. Furuse M., Fujita K., Hiiragi T., Fujimoto K., Tsukita S. Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol. 1998 Jun 29;141(7):1539–1550. doi: 10.1083/jcb.141.7.1539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Furuse M., Hirase T., Itoh M., Nagafuchi A., Yonemura S., Tsukita S., Tsukita S. Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol. 1993 Dec;123(6 Pt 2):1777–1788. doi: 10.1083/jcb.123.6.1777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gale N. W., Yancopoulos G. D. Growth factors acting via endothelial cell-specific receptor tyrosine kinases: VEGFs, angiopoietins, and ephrins in vascular development. Genes Dev. 1999 May 1;13(9):1055–1066. doi: 10.1101/gad.13.9.1055. [DOI] [PubMed] [Google Scholar]
  5. Gow A., Southwood C. M., Li J. S., Pariali M., Riordan G. P., Brodie S. E., Danias J., Bronstein J. M., Kachar B., Lazzarini R. A. CNS myelin and sertoli cell tight junction strands are absent in Osp/claudin-11 null mice. Cell. 1999 Dec 10;99(6):649–659. doi: 10.1016/s0092-8674(00)81553-6. [DOI] [PubMed] [Google Scholar]
  6. Hirase T., Staddon J. M., Saitou M., Ando-Akatsuka Y., Itoh M., Furuse M., Fujimoto K., Tsukita S., Rubin L. L. Occludin as a possible determinant of tight junction permeability in endothelial cells. J Cell Sci. 1997 Jul;110(Pt 14):1603–1613. doi: 10.1242/jcs.110.14.1603. [DOI] [PubMed] [Google Scholar]
  7. Kanda T., Iwasaki T., Yamawaki M., Tai T., Mizusawa H. Anti-GM1 antibody facilitates leakage in an in vitro blood-nerve barrier model. Neurology. 2000 Aug 22;55(4):585–587. doi: 10.1212/wnl.55.4.585. [DOI] [PubMed] [Google Scholar]
  8. Kanda T., Yamawaki M., Iwasaki T., Mizusawa H. Glycosphingolipid antibodies and blood-nerve barrier in autoimmune demyelinative neuropathy. Neurology. 2000 Apr 11;54(7):1459–1464. doi: 10.1212/wnl.54.7.1459. [DOI] [PubMed] [Google Scholar]
  9. Kanda Takashi, Yamawaki Masanaga, Mizusawa Hidehiro. Sera from Guillain-Barré patients enhance leakage in blood-nerve barrier model. Neurology. 2003 Jan 28;60(2):301–306. doi: 10.1212/01.wnl.0000041494.70178.17. [DOI] [PubMed] [Google Scholar]
  10. Kevil C. G., Payne D. K., Mire E., Alexander J. S. Vascular permeability factor/vascular endothelial cell growth factor-mediated permeability occurs through disorganization of endothelial junctional proteins. J Biol Chem. 1998 Jun 12;273(24):15099–15103. doi: 10.1074/jbc.273.24.15099. [DOI] [PubMed] [Google Scholar]
  11. Latker C. H., Wadhwani K. C., Balbo A., Rapoport S. I. Blood-nerve barrier in the frog during wallerian degeneration: are axons necessary for maintenance of barrier function? J Comp Neurol. 1991 Jun 22;308(4):650–664. doi: 10.1002/cne.903080410. [DOI] [PubMed] [Google Scholar]
  12. Lewis R. A., Sumner A. J. Electrophysiologic features of inherited demyelinating neuropathies: a reappraisal. Ann N Y Acad Sci. 1999 Sep 14;883:321–335. [PubMed] [Google Scholar]
  13. Mitic L. L., Anderson J. M. Molecular architecture of tight junctions. Annu Rev Physiol. 1998;60:121–142. doi: 10.1146/annurev.physiol.60.1.121. [DOI] [PubMed] [Google Scholar]
  14. Morita K., Furuse M., Fujimoto K., Tsukita S. Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands. Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):511–516. doi: 10.1073/pnas.96.2.511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Morita K., Sasaki H., Fujimoto K., Furuse M., Tsukita S. Claudin-11/OSP-based tight junctions of myelin sheaths in brain and Sertoli cells in testis. J Cell Biol. 1999 May 3;145(3):579–588. doi: 10.1083/jcb.145.3.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Morita K., Sasaki H., Furuse M., Tsukita S. Endothelial claudin: claudin-5/TMVCF constitutes tight junction strands in endothelial cells. J Cell Biol. 1999 Oct 4;147(1):185–194. doi: 10.1083/jcb.147.1.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nitta Takehiro, Hata Masaki, Gotoh Shimpei, Seo Yoshiteru, Sasaki Hiroyuki, Hashimoto Nobuo, Furuse Mikio, Tsukita Shoichiro. Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice. J Cell Biol. 2003 May 12;161(3):653–660. doi: 10.1083/jcb.200302070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Reese T. S., Karnovsky M. J. Fine structural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol. 1967 Jul;34(1):207–217. doi: 10.1083/jcb.34.1.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rubin L. L. Endothelial cells: adhesion and tight junctions. Curr Opin Cell Biol. 1992 Oct;4(5):830–833. doi: 10.1016/0955-0674(92)90107-n. [DOI] [PubMed] [Google Scholar]
  20. Saitou M., Ando-Akatsuka Y., Itoh M., Furuse M., Inazawa J., Fujimoto K., Tsukita S. Mammalian occludin in epithelial cells: its expression and subcellular distribution. Eur J Cell Biol. 1997 Jul;73(3):222–231. [PubMed] [Google Scholar]
  21. Saitou M., Fujimoto K., Doi Y., Itoh M., Fujimoto T., Furuse M., Takano H., Noda T., Tsukita S. Occludin-deficient embryonic stem cells can differentiate into polarized epithelial cells bearing tight junctions. J Cell Biol. 1998 Apr 20;141(2):397–408. doi: 10.1083/jcb.141.2.397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sharief M. K., Ingram D. A., Swash M. Circulating tumor necrosis factor-alpha correlates with electrodiagnostic abnormalities in Guillain-Barré syndrome. Ann Neurol. 1997 Jul;42(1):68–73. doi: 10.1002/ana.410420112. [DOI] [PubMed] [Google Scholar]
  23. Simon D. B., Lu Y., Choate K. A., Velazquez H., Al-Sabban E., Praga M., Casari G., Bettinelli A., Colussi G., Rodriguez-Soriano J. Paracellin-1, a renal tight junction protein required for paracellular Mg2+ resorption. Science. 1999 Jul 2;285(5424):103–106. doi: 10.1126/science.285.5424.103. [DOI] [PubMed] [Google Scholar]
  24. Stevenson B. R., Anderson J. M., Goodenough D. A., Mooseker M. S. Tight junction structure and ZO-1 content are identical in two strains of Madin-Darby canine kidney cells which differ in transepithelial resistance. J Cell Biol. 1988 Dec;107(6 Pt 1):2401–2408. doi: 10.1083/jcb.107.6.2401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tsukita S., Furuse M. Pores in the wall: claudins constitute tight junction strands containing aqueous pores. J Cell Biol. 2000 Apr 3;149(1):13–16. doi: 10.1083/jcb.149.1.13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wang W., Dentler W. L., Borchardt R. T. VEGF increases BMEC monolayer permeability by affecting occludin expression and tight junction assembly. Am J Physiol Heart Circ Physiol. 2001 Jan;280(1):H434–H440. doi: 10.1152/ajpheart.2001.280.1.H434. [DOI] [PubMed] [Google Scholar]
  27. Watanabe O., Arimura K., Kitajima I., Osame M., Maruyama I. Greatly raised vascular endothelial growth factor (VEGF) in POEMS syndrome. Lancet. 1996 Mar 9;347(9002):702–702. doi: 10.1016/s0140-6736(96)91261-1. [DOI] [PubMed] [Google Scholar]
  28. Zahraoui A., Louvard D., Galli T. Tight junction, a platform for trafficking and signaling protein complexes. J Cell Biol. 2000 Nov 27;151(5):F31–F36. doi: 10.1083/jcb.151.5.f31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Zhu J., Bai X. F., Mix E., Link H. Experimental allergic neuritis: cytolysin mRNA expression is upregulated in lymph node cells during convalescence. J Neuroimmunol. 1997 Sep;78(1-2):108–116. doi: 10.1016/s0165-5728(97)00087-8. [DOI] [PubMed] [Google Scholar]

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