The purpose of this study was to identify the receptor responsible for endocytosis of denatured collagen from blood. The major site of clearance of this material (at least 0.5 g/day in humans) is a receptor on liver sinusoidal endothelial cells (LSECs). We have now identified an 180-kDa endocytic receptor on LSECs, peptide mass fingerprinting of which revealed it to be the mannose receptor. Challenge of mannose-receptor knockout mice and their cultured LSECs revealed significantly reduced blood clearance and a complete absence of LSEC endocytosis of denatured collagen. Organ analysis of wild-type versus knockout mice after injection of denatured collagen revealed significantly reduced liver uptake in the knockout mice. Clearance/endocytosis of ligands for other receptors in these animals was as that for wild-type mice, and denatured collagen uptake in wild-type mice was not affected by other ligands of the mannose receptor, namely mannose and mannan. Furthermore, unlike that of mannose and mannan, endocytosis of denatured collagen by the mannose receptor is calcium independent. This suggests that the binding site for denatured collagen is distinct from that for mannose/mannan. Mannose receptors on LSECs appear to have less affinity for circulating triple helical type I collagen. Conclusion: The mannose receptor is the main candidate for being the endocytic denatured collagen receptor on LSECs. (HEPATOLOGY 2007;45:1454-1461
Liver sinusoidal endothelial cells (LSECs) play an essential role in systemic waste clearance by effective endocytosis of blood-borne waste macromolecules. We aimed to study LSECs' scavenger function during aging, and whether age-related morphological changes (eg, defenestration) affect this function, in F344/BN F1 rats. Endocytosis of the scavenger receptor ligand formaldehyde-treated serum albumin was significantly reduced in LSECs from old rats. Ligand degradation, LSEC protein expression of the major scavenger receptors for formaldehyde-treated serum albumin endocytosis, stabilin-1 and stabilin-2, and their staining patterns along liver sinusoids, was similar at young and old age, suggesting that other parts of the endocytic machinery are affected by aging. Formaldehyde-treated serum albumin uptake per cell, and cell porosity evaluated by electron microscopy, was not correlated, indicating that LSEC defenestration is not linked to impaired endocytosis. We report a significantly reduced LSEC endocytic capacity at old age, which may be especially important in situations with increased circulatory waste loads.
Liver sinusoidal endothelial cells (LSECs) are specialized scavenger cells that mediate high-capacity clearance of soluble waste macromolecules and colloid material, including blood-borne adenovirus. To explore if LSECs function as a sink for other viruses in blood, we studied the fate of virus-like particles (VLPs) of two ubiquitous human DNA viruses, BK and JC polyomavirus, in mice. Like complete virions, VLPs specifically bind to receptors and enter cells, but unlike complete virions, they cannot replicate. 125I-labeled VLPs were used to assess blood decay, organ-, and hepatocellular distribution of ligand, and non-labeled VLPs to examine cellular uptake by immunohisto- and -cytochemistry. BK- and JC-VLPs rapidly distributed to liver, with lesser uptake in kidney and spleen. Liver uptake was predominantly in LSECs. Blood half-life (∼1 min), and tissue distribution of JC-VLPs and two JC-VLP-mutants (L55F and S269F) that lack sialic acid binding affinity, were similar, indicating involvement of non-sialic acid receptors in cellular uptake. Liver uptake was not mediated by scavenger receptors. In spleen, the VLPs localized to the red pulp marginal zone reticuloendothelium, and in kidney to the endothelial lining of vasa recta segments, and the transitional epithelium of renal pelvis. Most VLP-positive vessels in renal medulla did not express PV-1/Meca 32, suggesting location to the non-fenestrated part of vasa recta. The endothelial cells of these vessels also efficiently endocytosed a scavenger receptor ligand, formaldehyde-denatured albumin, suggesting high endocytic activity compared to other renal endothelia. We conclude that LSECs very effectively cleared a large fraction of blood-borne BK- and JC-VLPs, indicating a central role of these cells in early removal of polyomavirus from the circulation. In addition, we report the novel finding that a subpopulation of endothelial cells in kidney, the main organ of polyomavirus persistence, showed selective and rapid uptake of VLPs, suggesting a role in viremic organ tropism.
Introduction The Norwegian research council supports the European cOAlition S, demanding that all scientific articles from the research they finance is openly available from 01.01.20211. Since 2013 the University of Oslo have mandatory institutional archiving of all peer reviewed articles in post-print version (after peer review)2. In 2019 several “publish and read” agreements were established between different publishers and the Norwegian higher education sector, enabling article processing charges to be paid by Norwegian universities and research institutions3. New agreements and changing regulations might be difficult to grasp by students, faculty and library employees. Aim is to test out basic knowledge about Open Access (OA) among beforementioned groups through a short, fun and informative OA event, while asking: Can a board game help promote Open Access? Method Choosing an existing OA board game was done based on the following considerations: it must have a recognizable concept and simple rules, be easy to administer, and not be too time consuming. Our choice is “The Game of Open Access”, a game produced by McGuinn and Spikin at University of Huddersfield, UK4. Modification of questions and answers to better fit a Norwegian context and publishing rules at the University of Oslo was essential. After testing of the game between us, minor alterations to the playing rules were added. Just as in the original game, for each correctly answered question, a participant keeps a card. After completing a round, the player gets a token representing a single published article, and then continues the game. The game is finished after all questions are answered correctly. The winner is the participant with the most points. Each card is worth three points and each token one point. These small modifications make the game more balanced and all participants equally involved. Before playing the game, a short (five minutes) introduction to OA in Norway with presentation of infographics is given. After the game, an evaluation form is administrated among all participants as an online questionnaire. Gameplaying time is approximately 30 minutes, which makes the game perfect for shorter events. Results Result from the evaluation form administered to librarians, students and faculty will be collected in the period September 2019-April 2020, in a range of different events. The first findings show that players are satisfied with board game content and questions, but they also suggest certain improvements Discussion Can a board game learning activity taking place outside of the ordinary library instructional courses for students and faculty at the University be an asset spreading awareness about Open Access? Does library staff have the basic understanding of the topic, or is further training needed?
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