Endothelial Cells Constituting Blood-nerve Barrier Have Highly Specialized Characteristics as Barrier-forming Cells

Abstract

ABSTRACT. In autoimmune disorders of the peripheral nervous system (PNS) such as Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy, breakdown of the blood-nerve barrier (BNB) has been considered as a key step in the disease process. Hence, it is important to know the cellular property of peripheral nerve microvascular endothelial cells (PnMECs) constituting the bulk of BNB. Although many in vitro models of the blood-brain barrier (BBB) have been established, very few in vitro BNB models have been reported so far. We isolated PnMECs from transgenic rats harboring the temperature-sensitive SV40 large T-antigen gene (tsA58 rat) and investigated the properties of these "barrier-forming cells". Isolated PnMECs (TR-BNBs) showed high transendothelial electrical resistance and expressed tight junction components and various types of influx as well as efflux transporters that have been reported to function at BBB. Furthermore, we confirmed the in vivo expression of various BBB-forming endothelial cell markers in the endoneurium of a rat sciatic nerve. These results suggest that PnMECs constituting the bulk of BNB have a highly specialized characteristic resembling the endothelial cells forming BBB.

Establishment and Characterization of Human Peripheral Nerve Microvascular Endothelial Cell Lines: A New <i>in vitro</i> Blood-Nerve Barrier (BNB) Model

“…We previously described that the same transporters were expressed in rat PnMECs (Sano et al, 2007). GLUT-1 and p-gp have been demonstrated to present on microvessels in the endoneurium of rat sciatic nerves by an immunohistochemical analysis (Sano et al, 2007). The FH-BNBs in the present study also expressed MDR-1, MRP-1 and GLUT-1.…”

“…Previous reports have indicated that PnMECs in human sural nerves express occludin, claudin-5 and ZO-1 (Kanda et al, 2004), and claudin-1 was detected in perineurium (Hirakawa et al, 2003), primary human PnMECs (Yosef et al, 2010) and human Schwann cells (Alanne et al, 2009). We also reported that rat PnMECs expressed many molecules forming tight junctions (Sano et al, 2007). FH-BNBs expressed all of the important molecules for maintaining tight junctions at the mRNA level, and contained occludin, claudin-5, ZO-1 and ZO-2 at the cell-cell boundaries at the protein level.…”

“…The glucose requirements of peripheral nerves have been also reported to be very high (Greene and Winegrad, 1979). We previously described that the same transporters were expressed in rat PnMECs (Sano et al, 2007). GLUT-1 and p-gp have been demonstrated to present on microvessels in the endoneurium of rat sciatic nerves by an immunohistochemical analysis (Sano et al, 2007).…”

“…Because PnMECs constitute the bulk of the BNB, in vitro studies using cultured PnMECs could be very useful to obtain a better understanding of the pathophysiology of these peripheral nerve disorders. However, only a few in vitro BNB models have been reported so far (Argall et al, 1994;Kanda et al, 1997;Iwasaki et al, 1999;Sano et al, 2007). This is probably due to the technical difficulties in isolating PnMECs from a peripheral nerve.…”

Advanced glycation end-products induce basement membrane hypertrophy in endoneurial microvessels and disrupt the blood–nerve barrier by stimulating the release of TGF-β and vascular endothelial growth factor (VEGF) by pericytes

“…Microangiopathy of the endoneurium is a common finding in the nerves of diabetic patients, and is thought to be a contributing factor to the development of diabetic neuropathy. The blood-nerve barrier (BNB) is localised in the microvessels of the endoneurium or perineurium, and consists of peripheral nerve microvascular endothelial cells (PnMECs), pericytes of endoneurial microvascular origin, and the basement membrane [1][2][3]. The basement membrane of the BNB plays important roles in maintaining the structure and function of capillary vessels [4].…”