Cellular localization of antiviral polyoxometalates in J774 macrophages.
The cellular localization of the polyoxometalates, K12H2[P2W12O48].24H20 (JM 1591), K10[P2W18-Zn4(H2O)2O68].20H2O (JM 1596), and [Me3NH]8[Si2W18Nb6O77] (JM 2820) were examined in cultured J774 cells by inhibition of cellular uptake of acetylated low-density lipoprotein (LDL) and by electron microscopy. All three polyoxometalates inhibited the cellular uptake of acetylated LDL, suggesting that the polyoxometalates block the association of acetylated LDL with cellular scavenger receptors. Fluorescence microscopy showed increased numbers of vacuoles in the presence of polyoxometalates, suggesting their uptake by cells. Using scanning electron microscopy (SEM), no significant cell surface morphological differences were observed between treated and non-treated J774 cells, suggesting that the compounds are not toxic to J774 cells up to a concentration of 200 micrograms/ml. Transmission electron microscopy (TEM) revealed large amounts of high electron dense granules were observed in the ramifying system of tubular cavities and vacuoles. TEM-energy dispersive spectroscopy (EDS) X-ray microanalysis was unable to differentiate the dense particles, most likely because the amount of tungsten in the cells was below the limit of detection. X-ray microanalysis conducted using the SEM-wavelength dispersive spectroscopy (WDS) detected tungsten, averaging 0.45 +/- 0.16% (mean +/- S.D.), in the J774 cells treated with JM 2820, suggesting that this polyoxometalate was taken up by the macrophages or was bound to their surface. Polyoxometalates interact at the cell surface and appear to be taken up by J774 macrophages. The cellular localization of polyoxometalates may be associated with anti-HIV activity.
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Department of Pharmaceutics, College of Pharmacy, University of Georgia, Athens 30602-2353, USA.
Greenspan
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Gutman
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Kelloes
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Farmer
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Boudinot
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D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics*; D002460:Cell Line; D004577:Electron Probe Microanalysis; D008077:Lipoproteins, LDL / Q000493:pharmacokinetics; D008264:Macrophages / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D017973:Tungsten Compounds / Q000493:pharmacokinetics*
D000998:Antiviral Agents; D008077:Lipoproteins, LDL; D009942:Organometallic Compounds; D017973:Tungsten Compounds; C087530:JM 1596; C087529:JM 2820; C087531:JM 1591