CELLULAR-LOCALIZATION OF ANTIVIRAL POLYOXOMETALATES IN J774 MACROPHAGES

The cellular localization of the polyoxometalates, K12H2[P2W12O48]. 24 H(2)O (JM 1591), K-10[P(2)W18Zn(4)(H2O)(2)O-68]. 20H(2)O (JM 1596), an d [Me(3)NH](8)[Si2W18Nb6O77] (JM 2820) were examined in cultured J774 cells by inhibition of cellular uptake of acetylated low-density lipop rotein (LDL) and by electron microscopy. All three polyoxometalates in hibited the cellular uptake of acetylated LDL, suggesting that the pol yoxometalates block the association of acetylated LDL with cellular sc avenger 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 ce ll surface morphological differences were observed between treated and non-treated J774 cells, suggesting that the compounds are not toxic t o J774 cells up to a concentration of 200 mu g/ml. Transmission electr on microscopy (TEM) revealed large amounts of high electron dense gran ules were observed in the ramifying system of tubular cavities and vac uoles. TEM-energy dispersive spectroscopy (EDS) X-ray microanalysis wa s unable to differentiate the dense particles, most likely because the amount of tungsten in the cells was below the limit of detection. X-r ay microanalysis conducted using a SEM-wavelength dispersive spectrosc opy (WDS) detected tungsten, averaging 0.45 +/- 0.16% (mean +/- S.D.), in the J774 cells treated with JM 2820, suggesting that this polyoxom etalate 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.