Endothelial cell monolayer permeability

Borges N, Shi F, Azevedo I, et al. Changes in brain microvessel endothelial cell monolayer permeability induced by adrenergic drugs. Eur J Pharmacol 1994 269 (2) 243-248. 

Table 6 Endothelial Cell Monolayer Permeability Transcellular and Paracellular Paths...

MV Shah, KL Audus, RT Borchardt. The application of bovine brain micro vessel endothelial-cell monolayers grown onto polycarbonate membranes in vitro to estimate the potential permeability of solutes through the blood-brain barrier. Pharm Res 6 624-627, 1989. 

Lai, B. K., Varma, S., Pappas, P. J., Hobson, R. W., and Duran, W. N. 2001. VEGF increases permeability of the endothelial cell monolayer by activation of PKB/akt, endothelial nitric-oxide synthase, and MAP kinase pathways. Microvasc. Res. 62 252-262. 

Two compounds had to be excluded from the data set. They were outliers (1.3 log units deviation) as also found in the analysis by Abraham et al. [26], It must also be remembered when considering the derived equations that log BB is a complex parameter that encompasses brain partitioning and permeability and may also depend on other processes such as metabolism, active transport, and so forth. Thus, the standard deviations of these determinations may fall within the range of the mean values. The authors could demonstrate that the derived equation could also estimate log BB outside of the training data set. Therefore, the value of the above correlation with the solvation free energy lies in its power to rank compounds for their ability to cross the blood-brain barrier before synthesis. Interestingly, it was also shown by Lombardo et al. [71] that the calculated AG°W correlated well with the determined permeability coefficient, PC, using endothelial cell monolayers from bovine brain mi-... 

Lindstrom, A.L., Erlandsen, S.L., Kersey, J.H. and Pennell, C.A. (1997) An in vitro model for toxin-mediated vascular leak syndrome ricin toxin A chain increases the permeability of human endothelial cell monolayers. Blood, 90, 2323. 

Suttorp N, Nolte A, Wilke A, Drenckhahn D Human neutrophil elastase increases permeability of cultured pulmonary endothelial cell monolayers. Int J Microcirc Clin Exp 1993 13 187-203. 

Huang AJ, Furie MB, Nicholson SC, Fischbaig J, Liebovitch LS, Silverstein SC Effects of human neutrophil chemotaxis across human endothelial cell monolayers on the permeability of these monolayers to ions and macroraolecules. J Cell Physiol 1988 135 355-366. 

Nakai, K., Sakuma, I., Ohta, T., Ando, J., Kitabatake, A., Nakazato, Y., and Takahashi, T.A. Permeability characteristics of hemoglobin derivatives across cultured endothelial cell monolayers., JLab Clin Med 132 313-319,1998. 

Esposito, C., Gerlach, H., Brett, J., Stem, D. and Vlassara, H. (1989). Endothelial receptor-mediated binding of glucose-modified albumin is associated with increased monolayer permeability and modulation of cell-surface coagulant properties. J. Exp. Med. 170, 1387-407. 

Freshly isolated or subcultured brain microvascular endothelial cells offer a notable in vitro tool to study drug transport across the blood-brain barrier. Cells can be grown to monolayers on culture plates or permeable membrane supports. The cells retain the major characteristics of brain endothelial cells in vivo, such as the morphology, specific biochemical markers of the blood-brain barrier, and the intercellular tight junctional network. Examples of these markers are y-glutamyl transpeptidase, alkaline phosphatase, von-Willebrandt factor-related antigen, and ZO-1 tight junctional protein. The methods of... 

Figure 2.5. Setup for in vitro measurement of blood-brain barrier permeability with a co-culture of bovine brain microvascular endothelial cells (BBMEC) and an astro ioma cell line, C6. The BBMEC are grown on top of a filter insert. The C6 cells are either grown on the opposite side of the filter or on the bottom of the wells. Transport across the BBMEC monolayer is measured by adding the test substance to the upper chamber and sampling from the lower chamber. The tightness of the monolayer is also characterized by the transendothelial electrical resistance (TEER). Courtesy of T. Abbruscato.

Table 4. In vitro endothelial permeability through an ECV 304 cell monolayer...

Permeability coefficients for paracellular diffusion of 3H-sucrose and 14C-inulin across monolayers of HCEC and immortalized SV-HCEC and transendothe-lial resistances have been compared to human lung microvascular endothelial cells to evaluate the BBB phenotype of the cerebromicrovascular endothelial cell cultures (Muruganandam et al. 1997). 

Oxidative stress damages endothelial cells of the BBB and contributes to vasogenic edema (Chan et al., 1984 Chan, 2001). Incubation of endothelial cells with ROS-generating systems increases the permeability of endothelial monolayers (Imaizumi et al., 1996 Lagrange et al., 1999 Fischer et al., 2005). The superoxide... 

Another method of Pgp regulation has been demonstrated by adrenomedullin (AM) (89). It is produced by endothelial cells in the brain and acts as a vasodilator in the cerebral circulation. It was shown that AM antisense decreased the transendo-thelial electrical resistance across endothelial monolayers. Treatment of these cells with AM activated Pgp, suggesting that AM acts as an autocrine mediator in the regulation of the properties of BBB endothelial cells. In addition, AM incubation decreased BBB permeability for sodium fluorescein (376 Da) but not for Evan s blue albumin (67 kDa). An interesting observation was that it also attenuated fluid-phase endocytosis. 

Modulation of the intercellular junctions by inhibiting the cadherin-cadherin interaction at the adherens junction has also been investigated. Peptides derived from the sequence of the extracellular domain of E-cadherin have been shown to modulate the intercellular junction of bovine brain microvessel endothelial cell (BBMEC) and Madin-Darby canine kidney (MDCK) cell monolayers. These peptides enhance the paracellular penetration of marker molecules such as 14C-mannitol and lower the transepithelial resistance of the monolayers.52 55 The use of these cadherin-derived peptides as adjuvants to enhance paracellular permeability of drugs is still under investigation. 

Cerebrovascular pathologies are abundant in Alzheimer s disease (AD) and are demonstrated by changes in the endothelium, amyloid depositions in the cerebral blood vessels, and disruption of the BBB. A possible mechanism that underlies this phenomenon may be drawn from in vitro studies using a BBB model of a monolayer of vascular endothelial cells. Amyloid (3-peptide, which deposits in plaques of AD patients, induced in these cells permeability to albumin and apoptotic cell death." The potential clinical relevance of this finding was emphasized by intracarotid infusion of amyloid (3-peptide, which resulted in BBB damage. ... 

Blanc, E.M., Toborek, M., Mark, R.J., Hennig, B., and Mattson, M.P., Amyloid beta-peptide induces cell monolayer albumin permeability, impairs glncose transport, and induces apoptosis in vascular endothelial cells, J. Neurochem., 68(5), 1870, 1997. 

Ffordijk PL, Anthony E, Mul FP, Rientsma R, Oomen LC, Roos D Vascular-endothelial-cadherin modulates endothelial monolayer permeability. J Cell Sci 1999 112 1915-1923. 

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