Abstract
Ultrastructural studies have shown that liver sinusoidal endothelial cells (LSECs) contain a cytoskeletal framework of filamentous actin, and that the presence of actin in the form of a calmodulin—actomyosin complex is responsible for regulation of the diameter of sinusoidal endothelial fenestrae (SEF). Rho has emerged as an important regulator of the actin cytoskeleton and consequently of cell morphology. We investigated actin filaments in relation to SEF in LSEC using heavy meromyosin decorated reaction and elucidated the roles of Rho and actin cytoskeleton in morphological and functional alterations of SEF. Second, according to intracytoplasmic Ca2+ concentration, plasma membrane Ca2+Mg2+-ATPase activities were clearly demonstrated on the outer surface of the labyrinth-like SEF in the isolated LSECs. Furthermore, by investigating intracytoplasmic Ca2+ concentration, we have demonstrated plasma membrane Ca2+-Mg2+-ATPase activities on the outer surface of the labyrinth-like SEF in the isolated LSECs. Currently, the majority of fenestral studies are focused on finding ways to increase the liver sieve’s porosity, which is reduced through pathological mechanisms.
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Wisse E (1970) An electron microscopic study of the fenestrated endothelial lining of rat liver sinusoids. J Ultrastruct Res 31:125–150
Wisse E, De Zanger RB, Jacobs R, McCuskey RS (1983) Scanning electron microscope observations on the structure of portal veins, sinusoids and central veins in rat liver. Scan Electron Microsc 3: 1441–1452
Braet F (2004) How molecular microscopy revealed new insights in the dynamics of hepatic endothelial fenestrae in the past decade. Liver Int 24:532–539
Babbs C, Haboubi NY, Mellor JM, Smith A, Rowan BP, Warnes TW (1990) Endothelial cell transformation in primary biliary cirrhosis: a morphological and biochemical study. Hepatology 11: 723–729
Fraser R, Dobbs BR, Rogers GWT (1995) Lipoproteins and the liver sieve: the role of the fenestrated sinusoidal endothelium in lipoprotein metabolism, atherosclerosis, and cirrhosis. Hepatology 21:863–874
Le Couteur DG, Fraser R, Cogger VC, McLean AJ (2002) Hepatic pseudocapillarisation and atherosclerosis in ageing. Lancet 359: 1612–1615
Liu P, Rudick M, Anderson RG (2002) Multiple functions of caveolin-1. J Biol Chem 277:41295–41298
Carafoli E (1987) Intracellular calcium homeostasis. Annu Rev Biochem 56:129–153
Fujimoto T (1993) Calcium pump of the plasma membrane is localized in caveolae. J Cell Biol 120:1147–1157
Bundgaard M, Hageman P, Crone C (1983) The three dimensional organization of plasmalemmal vesicular profiles in the endothelium of rat heart capillaries. Microvasc Res 25:358–368
Esser S, Wolburg K, Wolburg H, Breier G, Kurzchalia T, Risau W (1998) Vascular endothelial growth factor induces endothelial fenestration in vitro. J Cell Biol 140:947–959
Feng D, Nagy JA, Pyne K, Hammel, Dvorak HF, Dvorak A (1999) Pathways of macromolecular extravasation across microvascular endothelium in response to VPF/VEGF and other vasoactive mediators. Microcirculation 6:23–44
Ogi M, Yokomori H, Oda M, Nakamura M, Ishii H, Kamegaya Y, Motoori T (1998) A novel immunocytochemical staining method that preserves cell membranes: application for demonstrating Ca2+ pump-ATPase in the liver. Med Electron Microsc 31:100–108
Ogi M, Yokomori H, Kamegaya Y, Oda M, Ishii H (2000) Expression of plasma membrane Ca++-ATPase on hepatic sinusoidal endothelial fenestrae: modification of one step method. Med Electron Microsc 33:143–150
Yokomori H, Oda M, Ogi M, Kamegaya Y, Tsukada N, Nakamura M, Ishii H (2000) Hepatic sinusoidal endothelial fenestrae express plasma membrane Ca++pump and Ca++Mg++-ATPase. Liver 20: 458–464
Oda M, Nakamura M, Watanabe N, Ohya Y, Sekuzuka E, Tsukada N, Yonei Y, Komatsu H, Nagata H, Tsuchiya M (1983) Some dynamic aspects of the hepatic microcirculation: demonstration of sinusoidal endothelial fenestrae as a possible regulatory factor. In: Tsuchiya M, Wayland H, Oda M, Okazaki I (eds) Intravital observation of organ microcirculation. Excerpta Medica, Amsterdam, pp 105–138
Oda M, Tsukada N, Komatsu H, Kaneko K, Nakamura M, Tsuchiya M (1986) Electron microscopic localizations of actin, calmodulin and calcium in the hepatic sinusoidal endothelium in the rat. In: Kirn A, Knook DL, Wisse E (eds) Cells of the hepatic sinusoid, vol 1. Kupffer Cell Foundation, Rijswijk, pp 511–512
Van Der Smissen P, Van Bossuyt H, Charels K, Wisse E (1986) The structure and function of the cytoskeleton in sinusoidal endothelial cells in the rat liver. In: Kirn A, Knook DL, Wisse E (eds) Cells of the hepatic sinusoid, vol 1. Kupffer Cell Foundation, Rijswijk, pp 517–552
Oda M, Tsukada N, Komatsu H, Kaneko K, Nakamura M, Tsuchiya M (1986) Electron microscopic localizations of actin, calmodulin and calcium in the hepatic sinusoidal endothelium in the rat. In: Kirn A, Knook DL, Wisse E (eds) Cells of the hepatic sinusoid, vol 1. Kupffer Cell Foundation, Rijswijk, pp 511–512
Braet F, De Zanger R, Baekeland M, Crabbé E, Van Der Smissen P, Wisse E (1995) Structure and dynamics of the fenestrae-associated cytoskeleton of rat liver sinusoidal endothelial cells. Hepatology 21:180–189
Braet F, Spector I, De Zanger R, Wisse E (1998) A novel structure involved in the formation of liver endothelial cell fenestrae revealed using the actin inhibitor misakinolide. Proc Natl Acad Sci U S A 95:13635–13640
Braet F, Muller M, Vekemans K, Wisse E, Le Couteur DG (2003) Antimycin A-induced defenestration in rat hepatic sinusoidal endothelial cells. Hepatology 38:394–402
Nagai T, Yokomori H, Yoshimura K, Fujimaki K, Nomura M, Hibi T, Oda M (2004) Actin filaments around sinusoidal endothelial fenestrae in rat hepatic endothelial cells. Med Electron Microsc 2004;37:252–255
Nobes CD, Hall A (1995) Rho, Rac, and Cdc 42 GTPases regulate the assembly of multi-molecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 81: 53–62
Yokomori H, Yoshimura K, Funakoshi S, Nagai T, Fujimaki K, Nomura M, Ishii H, Oda M (2004) Rho modulates hepatic sinusoidal endothelial fenestrae via regulation of the actin cytoskeleton in rat endothelial cells. Lab Invest 84:857–864
Tsukada N, Azuma T, Phillips MJ (1994) Isolation of the bile canalicular actin-myosin II motor. Proc Natl Acad Sci U S A 91:6919–6923
Le Couteur DG, Cogger VC, Markus AM, Harvey PJ, Yin ZL, Annselin AD, McLean AJ (2001) Pseudocapillarization and associated energy limitation in the aged rat liver. Hepatology 33:537–543
Deleve LD, Wang X, Hu L, McCuskey MK, McCuskey RS (2004) Rat liver sinusoidal endothelial cell phenotype is maintained by paracrine and autocrine regulation. Am J Physiol Gastrointest Liver Physiol 287:G757–G763
Saito M, Matsuura T, Nagatsuma K, Tanaka K, Maehashi H, Shimizu K, Hataba Y, Kato F, Kashimori I, Tajiri H, Braet F (2007) The functional interrelationship between gap junctions and fenestrae in endothelial cells of the liver organoid. J Membr Biol 14: 1424–1432
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Dr. Hiroaki Yokomori, of the Department of Internal Medicine, Kitasato Medical Center Hospital, Saitama, Japan, is the winner of the Japanese Society for Clinical Molecular Morphology Award for Promoting Young Researchers in 2007. Dr. Yokomori was recognized for his great contribution in elucidating the role of sinusoidal endothelial fenestrae in the physiology and pathology of the liver.
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Yokomori, H. New insights into the dynamics of sinusoidal endothelial fenestrae in liver sinusoidal endothelial cells. Med Mol Morphol 41, 1–4 (2008). https://doi.org/10.1007/s00795-007-0390-7
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DOI: https://doi.org/10.1007/s00795-007-0390-7