Liver sinusoidal endothelial cells show reduced scavenger function and downregulation of Fc gamma receptor IIb, yet maintain a preserved fenestration in the Glmp.sup.gt/gt mouse model of slowly progressing liver fibrosis
Liver sinusoidal endothelial cells (LSECs) are fenestrated endothelial cells with a unique, high endocytic clearance capacity for blood-borne waste macromolecules and colloids. This LSEC scavenger function has been insufficiently characterized in liver disease. The Glmp.sup.gt/gt mouse lacks express...
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| Veröffentlicht in: | PloS one 2023-11, Vol.18 (11), p.e0293526 |
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| creator | Antwi, Milton Boaheng Dumitriu, Gianina Simón-Santamaria, Jaione Romano, Javier Sánchez Li, Ruomei Smedsrød, Bård Vik, Anders Eskild, Winnie Sørensen, Karen Kristine |
| description | Liver sinusoidal endothelial cells (LSECs) are fenestrated endothelial cells with a unique, high endocytic clearance capacity for blood-borne waste macromolecules and colloids. This LSEC scavenger function has been insufficiently characterized in liver disease. The Glmp.sup.gt/gt mouse lacks expression of a subunit of the MFSD1/GLMP lysosomal membrane protein transporter complex, is born normal, but soon develops chronic, mild hepatocyte injury, leading to slowly progressing periportal liver fibrosis, and splenomegaly. This study examined how LSEC scavenger function and morphology are affected in the Glmp.sup.gt/gt model. FITC-labelled formaldehyde-treated serum albumin (FITC-FSA), a model ligand for LSEC scavenger receptors was administered intravenously into Glmp.sup.gt/gt mice, aged 4 months (peak of liver inflammation), 9-10 month, and age-matched Glmp.sup.wt/wt mice. Organs were harvested for light and electron microscopy, quantitative image analysis of ligand uptake, collagen accumulation, LSEC ultrastructure, and endocytosis receptor expression (also examined by qPCR and western blot). In both age groups, the Glmp.sup.gt/gt mice showed multifocal liver injury and fibrosis. The uptake of FITC-FSA in LSECs was significantly reduced in Glmp.sup.gt/gt compared to wild-type mice. Expression of LSEC receptors stabilin-1 (Stab1), and mannose receptor (Mcr1) was almost similar in liver of Glmp.sup.gt/gt mice and age-matched controls. At the same time, immunostaining revealed differences in the stabilin-1 expression pattern in sinusoids and accumulation of stabilin-1-positive macrophages in Glmp.sup.gt/gt liver. Fc[gamma]RIIb (Fcgr2b), which mediates LSEC endocytosis of soluble immune complexes was widely and significantly downregulated in Glmp.sup.gt/gt liver. Despite increased collagen in space of Disse, LSECs of Glmp.sup.gt/gt mice showed well-preserved fenestrae organized in sieve plates but the frequency of holes >400 nm in diameter was increased, especially in areas with hepatocyte damage. In both genotypes, FITC-FSA also distributed to endothelial cells of spleen and bone marrow sinusoids, suggesting that these locations may function as possible compensatory sites of clearance of blood-borne scavenger receptor ligands in liver fibrosis. |
| doi_str_mv | 10.1371/journal.pone.0293526 |
| format | Article |
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This LSEC scavenger function has been insufficiently characterized in liver disease. The Glmp.sup.gt/gt mouse lacks expression of a subunit of the MFSD1/GLMP lysosomal membrane protein transporter complex, is born normal, but soon develops chronic, mild hepatocyte injury, leading to slowly progressing periportal liver fibrosis, and splenomegaly. This study examined how LSEC scavenger function and morphology are affected in the Glmp.sup.gt/gt model. FITC-labelled formaldehyde-treated serum albumin (FITC-FSA), a model ligand for LSEC scavenger receptors was administered intravenously into Glmp.sup.gt/gt mice, aged 4 months (peak of liver inflammation), 9-10 month, and age-matched Glmp.sup.wt/wt mice. Organs were harvested for light and electron microscopy, quantitative image analysis of ligand uptake, collagen accumulation, LSEC ultrastructure, and endocytosis receptor expression (also examined by qPCR and western blot). In both age groups, the Glmp.sup.gt/gt mice showed multifocal liver injury and fibrosis. The uptake of FITC-FSA in LSECs was significantly reduced in Glmp.sup.gt/gt compared to wild-type mice. Expression of LSEC receptors stabilin-1 (Stab1), and mannose receptor (Mcr1) was almost similar in liver of Glmp.sup.gt/gt mice and age-matched controls. At the same time, immunostaining revealed differences in the stabilin-1 expression pattern in sinusoids and accumulation of stabilin-1-positive macrophages in Glmp.sup.gt/gt liver. Fc[gamma]RIIb (Fcgr2b), which mediates LSEC endocytosis of soluble immune complexes was widely and significantly downregulated in Glmp.sup.gt/gt liver. Despite increased collagen in space of Disse, LSECs of Glmp.sup.gt/gt mice showed well-preserved fenestrae organized in sieve plates but the frequency of holes >400 nm in diameter was increased, especially in areas with hepatocyte damage. In both genotypes, FITC-FSA also distributed to endothelial cells of spleen and bone marrow sinusoids, suggesting that these locations may function as possible compensatory sites of clearance of blood-borne scavenger receptor ligands in liver fibrosis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0293526</identifier><language>eng</language><publisher>Public Library of Science</publisher><subject>Albumin ; Biotechnology industry ; Care and treatment ; Collagen ; Computer software industry ; Diagnosis ; Endothelium ; Equipment and supplies ; Fc receptors ; Fibrosis ; Formaldehyde ; Health aspects ; Image processing ; Liver diseases ; Monosaccharides ; Scientific equipment and supplies industry ; Sugars</subject><ispartof>PloS one, 2023-11, Vol.18 (11), p.e0293526</ispartof><rights>COPYRIGHT 2023 Public Library of Science</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,864,27923,27924</link.rule.ids></links><search><creatorcontrib>Antwi, Milton Boaheng</creatorcontrib><creatorcontrib>Dumitriu, Gianina</creatorcontrib><creatorcontrib>Simón-Santamaria, Jaione</creatorcontrib><creatorcontrib>Romano, Javier Sánchez</creatorcontrib><creatorcontrib>Li, Ruomei</creatorcontrib><creatorcontrib>Smedsrød, Bård</creatorcontrib><creatorcontrib>Vik, Anders</creatorcontrib><creatorcontrib>Eskild, Winnie</creatorcontrib><creatorcontrib>Sørensen, Karen Kristine</creatorcontrib><title>Liver sinusoidal endothelial cells show reduced scavenger function and downregulation of Fc gamma receptor IIb, yet maintain a preserved fenestration in the Glmp.sup.gt/gt mouse model of slowly progressing liver fibrosis</title><title>PloS one</title><description>Liver sinusoidal endothelial cells (LSECs) are fenestrated endothelial cells with a unique, high endocytic clearance capacity for blood-borne waste macromolecules and colloids. This LSEC scavenger function has been insufficiently characterized in liver disease. The Glmp.sup.gt/gt mouse lacks expression of a subunit of the MFSD1/GLMP lysosomal membrane protein transporter complex, is born normal, but soon develops chronic, mild hepatocyte injury, leading to slowly progressing periportal liver fibrosis, and splenomegaly. This study examined how LSEC scavenger function and morphology are affected in the Glmp.sup.gt/gt model. FITC-labelled formaldehyde-treated serum albumin (FITC-FSA), a model ligand for LSEC scavenger receptors was administered intravenously into Glmp.sup.gt/gt mice, aged 4 months (peak of liver inflammation), 9-10 month, and age-matched Glmp.sup.wt/wt mice. Organs were harvested for light and electron microscopy, quantitative image analysis of ligand uptake, collagen accumulation, LSEC ultrastructure, and endocytosis receptor expression (also examined by qPCR and western blot). In both age groups, the Glmp.sup.gt/gt mice showed multifocal liver injury and fibrosis. The uptake of FITC-FSA in LSECs was significantly reduced in Glmp.sup.gt/gt compared to wild-type mice. Expression of LSEC receptors stabilin-1 (Stab1), and mannose receptor (Mcr1) was almost similar in liver of Glmp.sup.gt/gt mice and age-matched controls. At the same time, immunostaining revealed differences in the stabilin-1 expression pattern in sinusoids and accumulation of stabilin-1-positive macrophages in Glmp.sup.gt/gt liver. Fc[gamma]RIIb (Fcgr2b), which mediates LSEC endocytosis of soluble immune complexes was widely and significantly downregulated in Glmp.sup.gt/gt liver. Despite increased collagen in space of Disse, LSECs of Glmp.sup.gt/gt mice showed well-preserved fenestrae organized in sieve plates but the frequency of holes >400 nm in diameter was increased, especially in areas with hepatocyte damage. In both genotypes, FITC-FSA also distributed to endothelial cells of spleen and bone marrow sinusoids, suggesting that these locations may function as possible compensatory sites of clearance of blood-borne scavenger receptor ligands in liver fibrosis.</description><subject>Albumin</subject><subject>Biotechnology industry</subject><subject>Care and treatment</subject><subject>Collagen</subject><subject>Computer software industry</subject><subject>Diagnosis</subject><subject>Endothelium</subject><subject>Equipment and supplies</subject><subject>Fc receptors</subject><subject>Fibrosis</subject><subject>Formaldehyde</subject><subject>Health aspects</subject><subject>Image processing</subject><subject>Liver diseases</subject><subject>Monosaccharides</subject><subject>Scientific equipment and supplies industry</subject><subject>Sugars</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNqNkdtqGzEQhpfSQtO0b9ALQaFQqDfSyqv1XoaQpAZDoKdbo8OsrKCVFo3Wbt61D1Ml6YUNvShCmmH0_b80UlW9Z7RmvGMX93FOQfp6igFq2vS8bcSL6oz1vFmIhvKXR_nr6g3iPaUtXwlxVv3euD0kgi7MGJ2RnkAwMe_Au5Jr8B4J7uKBJDCzBkNQyz0EWzTDHHR2MRAZDDHxEBLY2cunUhzIjSZWjqMsSg1Tjoms1-ozeYBMRulCLpNIMiVASPtiPEAAzOlZX_bKHcitH6ca56m2-cIWXZwRymrAP56APh78Q7GItriUFizxT90MTqWIDt9WrwbpEd79jefVj5vr71dfFpu72_XV5WZhmRBisZItA6aUXgllegWtoUvF1BKA005p3nAmWg5LAV1nZD_IJe1XvKXQSKEYN_y8-vDsa6WHrQtDLH3o0aHeXnYdY1SIXhSq_gdVhoHR6fJ1gyv1E8GnE0FhMvzKVs6I2_W3r__P3v08ZT8esTuQPu8w-vnx5fEY_AM8tsFC</recordid><startdate>20231101</startdate><enddate>20231101</enddate><creator>Antwi, Milton Boaheng</creator><creator>Dumitriu, Gianina</creator><creator>Simón-Santamaria, Jaione</creator><creator>Romano, Javier Sánchez</creator><creator>Li, Ruomei</creator><creator>Smedsrød, Bård</creator><creator>Vik, Anders</creator><creator>Eskild, Winnie</creator><creator>Sørensen, Karen Kristine</creator><general>Public Library of Science</general><scope>IOV</scope><scope>ISR</scope></search><sort><creationdate>20231101</creationdate><title>Liver sinusoidal endothelial cells show reduced scavenger function and downregulation of Fc gamma receptor IIb, yet maintain a preserved fenestration in the Glmp.sup.gt/gt mouse model of slowly progressing liver fibrosis</title><author>Antwi, Milton Boaheng ; Dumitriu, Gianina ; Simón-Santamaria, Jaione ; Romano, Javier Sánchez ; Li, Ruomei ; Smedsrød, Bård ; Vik, Anders ; Eskild, Winnie ; Sørensen, Karen Kristine</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g1666-8a51e1bbc86bd9be5d04b1b4ee307bc3231653e46e77da9fa4098350e2a6b13d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Albumin</topic><topic>Biotechnology industry</topic><topic>Care and treatment</topic><topic>Collagen</topic><topic>Computer software industry</topic><topic>Diagnosis</topic><topic>Endothelium</topic><topic>Equipment and supplies</topic><topic>Fc receptors</topic><topic>Fibrosis</topic><topic>Formaldehyde</topic><topic>Health aspects</topic><topic>Image processing</topic><topic>Liver diseases</topic><topic>Monosaccharides</topic><topic>Scientific equipment and supplies industry</topic><topic>Sugars</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Antwi, Milton Boaheng</creatorcontrib><creatorcontrib>Dumitriu, Gianina</creatorcontrib><creatorcontrib>Simón-Santamaria, Jaione</creatorcontrib><creatorcontrib>Romano, Javier Sánchez</creatorcontrib><creatorcontrib>Li, Ruomei</creatorcontrib><creatorcontrib>Smedsrød, Bård</creatorcontrib><creatorcontrib>Vik, Anders</creatorcontrib><creatorcontrib>Eskild, Winnie</creatorcontrib><creatorcontrib>Sørensen, Karen Kristine</creatorcontrib><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Antwi, Milton Boaheng</au><au>Dumitriu, Gianina</au><au>Simón-Santamaria, Jaione</au><au>Romano, Javier Sánchez</au><au>Li, Ruomei</au><au>Smedsrød, Bård</au><au>Vik, Anders</au><au>Eskild, Winnie</au><au>Sørensen, Karen Kristine</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Liver sinusoidal endothelial cells show reduced scavenger function and downregulation of Fc gamma receptor IIb, yet maintain a preserved fenestration in the Glmp.sup.gt/gt mouse model of slowly progressing liver fibrosis</atitle><jtitle>PloS one</jtitle><date>2023-11-01</date><risdate>2023</risdate><volume>18</volume><issue>11</issue><spage>e0293526</spage><pages>e0293526-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Liver sinusoidal endothelial cells (LSECs) are fenestrated endothelial cells with a unique, high endocytic clearance capacity for blood-borne waste macromolecules and colloids. This LSEC scavenger function has been insufficiently characterized in liver disease. The Glmp.sup.gt/gt mouse lacks expression of a subunit of the MFSD1/GLMP lysosomal membrane protein transporter complex, is born normal, but soon develops chronic, mild hepatocyte injury, leading to slowly progressing periportal liver fibrosis, and splenomegaly. This study examined how LSEC scavenger function and morphology are affected in the Glmp.sup.gt/gt model. FITC-labelled formaldehyde-treated serum albumin (FITC-FSA), a model ligand for LSEC scavenger receptors was administered intravenously into Glmp.sup.gt/gt mice, aged 4 months (peak of liver inflammation), 9-10 month, and age-matched Glmp.sup.wt/wt mice. Organs were harvested for light and electron microscopy, quantitative image analysis of ligand uptake, collagen accumulation, LSEC ultrastructure, and endocytosis receptor expression (also examined by qPCR and western blot). In both age groups, the Glmp.sup.gt/gt mice showed multifocal liver injury and fibrosis. The uptake of FITC-FSA in LSECs was significantly reduced in Glmp.sup.gt/gt compared to wild-type mice. Expression of LSEC receptors stabilin-1 (Stab1), and mannose receptor (Mcr1) was almost similar in liver of Glmp.sup.gt/gt mice and age-matched controls. At the same time, immunostaining revealed differences in the stabilin-1 expression pattern in sinusoids and accumulation of stabilin-1-positive macrophages in Glmp.sup.gt/gt liver. Fc[gamma]RIIb (Fcgr2b), which mediates LSEC endocytosis of soluble immune complexes was widely and significantly downregulated in Glmp.sup.gt/gt liver. Despite increased collagen in space of Disse, LSECs of Glmp.sup.gt/gt mice showed well-preserved fenestrae organized in sieve plates but the frequency of holes >400 nm in diameter was increased, especially in areas with hepatocyte damage. In both genotypes, FITC-FSA also distributed to endothelial cells of spleen and bone marrow sinusoids, suggesting that these locations may function as possible compensatory sites of clearance of blood-borne scavenger receptor ligands in liver fibrosis.</abstract><pub>Public Library of Science</pub><doi>10.1371/journal.pone.0293526</doi><tpages>e0293526</tpages></addata></record> |
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| subjects | Albumin Biotechnology industry Care and treatment Collagen Computer software industry Diagnosis Endothelium Equipment and supplies Fc receptors Fibrosis Formaldehyde Health aspects Image processing Liver diseases Monosaccharides Scientific equipment and supplies industry Sugars |
| title | Liver sinusoidal endothelial cells show reduced scavenger function and downregulation of Fc gamma receptor IIb, yet maintain a preserved fenestration in the Glmp.sup.gt/gt mouse model of slowly progressing liver fibrosis |
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