Rapid and Efficient Clearance of Blood-borne Virus by Liver Sinusoidal Endothelium
The liver removes quickly the great bulk of virus circulating in blood, leaving only a small fraction to infect the host, in a manner characteristic of each virus. The scavenger cells of the liver sinusoids are implicated, but the mechanism is entirely unknown. Here we show, borrowing a mouse model of adenovirus clearance, that nearly all infused adenovirus is cleared by the liver sinusoidal endothelial cell (LSEC). Using refined immunofluorescence microscopy techniques for distinguishing macrophages and endothelial cells in fixed liver, and identifying virus by two distinct physicochemical methods, we localized adenovirus 1 minute after infusion mainly to the LSEC (∼90%), finding ∼10% with Kupffer cells (KC) and none with hepatocytes. Electron microscopy confirmed our results. In contrast with much prior work claiming the main scavenger to be the KC, our results locate the clearance mechanism to the LSEC and identify this cell as a key site of antiviral activity.
Vyšlo v časopise:
Rapid and Efficient Clearance of Blood-borne Virus by Liver Sinusoidal Endothelium. PLoS Pathog 7(9): e32767. doi:10.1371/journal.ppat.1002281
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1002281
Souhrn
The liver removes quickly the great bulk of virus circulating in blood, leaving only a small fraction to infect the host, in a manner characteristic of each virus. The scavenger cells of the liver sinusoids are implicated, but the mechanism is entirely unknown. Here we show, borrowing a mouse model of adenovirus clearance, that nearly all infused adenovirus is cleared by the liver sinusoidal endothelial cell (LSEC). Using refined immunofluorescence microscopy techniques for distinguishing macrophages and endothelial cells in fixed liver, and identifying virus by two distinct physicochemical methods, we localized adenovirus 1 minute after infusion mainly to the LSEC (∼90%), finding ∼10% with Kupffer cells (KC) and none with hepatocytes. Electron microscopy confirmed our results. In contrast with much prior work claiming the main scavenger to be the KC, our results locate the clearance mechanism to the LSEC and identify this cell as a key site of antiviral activity.
Zdroje
1. MimsCA 1959 The response of mice to large intravenous injections of ectromelia virus. I. The fate of injected virus. Br J Exp Pathol 40 533 542
2. BrunnerKTHurezDMcCluskeyRTBenacerrafB 1960 Blood Clearance of P32-Labeled Vesicular Stomatitis and Newcastle Disease Viruses by the Reticuloendothelial System in Mice. J Immunol 85 99 105
3. AlemanyRSuzukiKCurielDT 2000 Blood clearance rates of adenovirus type 5 in mice. J Gen Virol 81 2605 2609
4. WorgallSWolffGFalck-PedersenECrystalRG 1997 Innate immune mechanisms dominate elimination of adenoviral vectors following in vivo administration. Hum Gene Ther 8 37 44
5. ZhangLDaileyPJGettieABlanchardJHoDD 2002 The liver is a major organ for clearing simian immunodeficiency virus in rhesus monkeys. J Virol 76 5271 5273
6. MimsCA 1964 Aspects of the pathogenesis of virus diseases. Bacteriol Rev 28 30 71
7. SackBKHerzogRW 2009 Evading the immune response upon in vivo gene therapy with viral vectors. Curr Opin Mol Ther 11 493 503
8. BarryMAHofherrSEChenCYSenacJSHillestadMLShashkovaEV 2009 Systemic delivery of therapeutic viruses. Curr Opin Mol Ther 11 411 420
9. HaismaHJBoesjesMBeerensAMvan der StrateBWCurielDTPluddemannAGordonSBelluAR 2009 Scavenger receptor A: a new route for adenovirus 5. Mol Pharm 6 366 374
10. SimonVHoDD 2003 HIV-1 dynamics in vivo: Implications for therapy. Nat Rev Microbiol 1 181 190
11. SmedsrodBPertoftHGustafsonSLaurentTC 1990 Scavenger functions of the liver endothelial cell. Biochem J 266 313 327
12. ElvevoldKSmedsrodBMartinezI 2008 The liver sinusoidal endothelial cell: a cell type of controversial and confusing identity. Am J Physiol Gastrointest Liver Physiol 294 G391 G400
13. Nakamura-IshizuAMorikawaSShimizuKEzakiT 2008 Characterization of sinusoidal endothelial cells of the liver and bone marrow using an intravital lectin injection method. J Mol Hist 39 471 479
14. KnollePAGermannTTreichelUUhrigASchmittE 1999 Endotoxin down-regulates T cell activation by antigen-presenting liver sinusoidal endothelial cells. J Immunol 162 1401 1407
15. HuebertRCJagaveluKLieblAFHuangBQSplinterPL 2010 Immortalized liver endothelial cells: a cell culture model for studies of motility and angiogenesis. Lab Invest 90 1770 81
16. ZellwegerRMPrestwoodTRShrestaS 2010 Enhanced infection of liver sinusoidal endothelial cells in a mouse model of antibody-induced severe dengue disease. Cell Host Microbe 7 128 139
17. PertoftHSmedsrodB 1987 Separation and characterization of liver cells. PretlowTGIIPretlowTP Cell separation: Methods and selected applications Orlando Academic Press 1 24
18. AschoffL 1924 Reticuloendothelial System (Janeway Lecture, New York). Lectures on Pathology (delivered in the United States, 1924) New York Paul B. Hoeber, Inc 1 33
19. Van FurthRCohnZAHirschJGHumphreyJHSpectorWG 1972 The mononuclear phagocyte system: a new classification of macrophages, monocytes, and their precursor cells. Bull World Health Organ 46 845 852
20. FawcettDW 1986 Bloom and Fawcett. A Textbook of Histology Philadelphia W.B.Saunders Company
21. NathansonNTylerKL 1997 Entry, dissemination, shedding, and transmission of viruses. NathansonN Viral Pathogenesis Lippincott Williams and Wilkins 13 32
22. StewartCC 1984 From the Editor. J Leuk Biol 35 front matter
23. KawaiYSmedsrodBElvevoldKWakeK 1998 Uptake of lithium carmine by sinusoidal endothelial and Kupffer cells of the rat liver: new insights into the classical vital staining and the reticulo-endothelial system. Cell Tissue Res 292 395 410
24. WakeKKawaiYSmedsrodB 2001 Re-evaluation of the reticulo-endothelial system. Ital J Anat Embryol 106 261 269
25. MuroHShirasawaHMaedaMNakamuraS 1987 Fc receptors of liver sinusoidal endothelium in normal rats and humans. Gastroenterology 93 1078 1085
26. MousaviSASporstolMFladebyCKjekenRBaroisN 2007 Receptor-Mediated Endocytosis of Immune Complexes in Rat Liver Sinusoidal Endothelial Cells Is Mediated by FcRIIb2. Hepatology 46 871 884
27. MellmanI 1996 Endocytosis and molecular sorting. Annu Rev Cell Dev Biol 12 575 625
28. ClarkKRLiuXMcGrathJPJohnsonPR 1999 Highly purified recombinant adeno-associated virus vectors are biologically active and free of detectable helper and wild-type viruses. Hum Gene Ther 10 1031 1039
29. PalmerDJNgP 2004 Physical and infectious titers of helper-dependent adenoviral vectors: a method of direct comparison to the adenovirus reference material. Mol Ther 10 792 798
30. VachaJ 1975 Blood volume in inbred strain BALB/c, CBA/J and C57BL/10 mice determined by means of 59Fe-labelled red cells and 59Fe bound to transferrin. Physiol Bohemoslov 24 113 119
31. LeopoldPLFerrisBGrinbergIWorgallSHackettNR 1998 Fluorescent virions: Dynamic tracking of the pathway of adenoviral gene transfer vectors in living cells. Hum Gen Ther 9 367 378
32. ValentineRCPereiraHG 1965 Antigens and structure of the adenovirus. J Mol Biol 13 1 20
33. XieJChiangLContrerasJWuKGarnerJA 2006 Novel fiber-dependent entry mechanism for adenovirus serotype 5 in lacrimal acini. J Virol 80 11833 11851
34. LydenTWAndersonCLRobinsonJM 2002 The endothelium but not the syncytiotrophoblast of human placenta expresses caveolae. Placenta 23 640 652
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Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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