RESUMEN
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 (â¼1 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.
Asunto(s)
Riñón/irrigación sanguínea , Riñón/virología , Hígado/virología , Virión/fisiología , Animales , Virus BK/metabolismo , Células Cultivadas , Células Endoteliales/virología , Virus JC/metabolismo , Hígado/citología , Ratones , Ratones Endogámicos C57BL , Ácido N-Acetilneuramínico/metabolismo , Virión/químicaRESUMEN
The red king crab Paralithodes camtschaticus was introduced to the Barents Sea from the North Pacific in the 1960s. A previous study concluded that it may be indirectly responsible for increased transmission of Trypanosoma murmanense to cod Gadus morhua in the southern Barents Sea by promoting an increase in the population of the leech vector Johanssonia arctica. Eleven species of fish, totalling 681 individuals, caught in October 2002 along the coast of Finnmark, were examined for trypanosome infections. The aims were to investigate changes in levels of infection in cod since 1999-2001, and to extend the sampling to other fish species. Relatively high infection levels were found in cod, haddock Melanogrammus aeglefinus and long rough dab Hippoglossoides platessoides, while other species were lightly infected or uninfected. In cod, no significant geographical differences in levels of infection were found, but haddock were significantly more heavily infected in western Finnmark.
Asunto(s)
Anomuros/parasitología , Enfermedades de los Peces/epidemiología , Peces/parasitología , Tripanosomiasis/veterinaria , Animales , Gadiformes/parasitología , Especies Introducidas , Tripanosomiasis/epidemiología , Tripanosomiasis/transmisiónRESUMEN
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.
Asunto(s)
Envejecimiento/metabolismo , Endocitosis , Células Endoteliales/metabolismo , Hígado/citología , Animales , Moléculas de Adhesión Celular Neuronal/metabolismo , Células Cultivadas , Formaldehído/metabolismo , Hígado/ultraestructura , Masculino , Microscopía Confocal , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Ratas , Ratas Endogámicas F344 , Receptores de Superficie Celular/metabolismo , Albúmina Sérica Bovina/metabolismoRESUMEN
UNLABELLED: 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.