Cell biology of blood-nerve barrier, using cultured endothelial cell of endoneurial microvessel origin

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Penetration of immunoglobulins and/or migration of activated lymphocytes into peripheral nervous system (PNS) parenchyma are the initial key steps to develop immunological disorders of PNS including Guillain-Barre syndrome, IgM neuropathy and chronic inflammatory demyelinating polyradiculoneuropathy. Hence, it is important to know the cellular property of endothelial cells of endoneurial tissue origin (PnMEC) because these cells constitute the bulk of the blood-nerve barrier (BNB). For this purpose we developed a method to isolate and culture pure populations of PnMECs from bovine cauda equina (Kanda T et al., J Neurosci Res 1997) and then established the technique to form in vitro BNB model. Using the BNB in vitro model, we found : (1) endoneurial pericytes enhance the barrier function of this model and may be essential for the BNB integrity (Iwasaki T et al., J Med Dent Sci 1999) ; (2) Various cytokines including VEGF, IL-1 beta, TNF alpha, and TGF beta, which are supposed to play key role in the development of inflammatory neuropathies, are found to decrease the membrane resistance and increase the radioactive tracer (inulin) through this model ; (3) Anti-GM1 monoclonal antibody also weaken the BNB function (Kanda T et al., submitted). Further experiments using sera of neuropathy patients and those to clarify signaling pathways underlying loosening of the BNB following exposure to anti-GM1 antibody are underway.