EFFECTS OF BISPHOSPHONATE DERIVATIVES ON MACROPHAGE FUNCTION

The effects of three bisphosphonates (BPs), designated 4-amino-1-hydro xybutylidene-1, 1-bisphosphonate (AHBuBP), 6-amino-1-hydroxylidene-1, 1-bisphosphonate (AHHexBP) and chloromethylenebisphosphonate (Cl(2)MBP ), were evaluated on the basis of their effect on the phagocytic activ ity, lysosomal enzyme release and superoxide anion production in the r at peritoneal macrophage (M Phi). AHBuBP was found to inhibit in a con centration-dependent manner the phagocytosis of sheep red blood cells (SRBC). The same activity was seen with the phagocytosis of latex bead s, although this effect was independent of calcium concentration. Conv ersely, AHHexBP and Cl(2)MBP were weak inhibitors of phagocytosis of b oth SRBC and latex beads. Inhibition studies on the phorbol myristate acetate-stimulated production of superoxide anion have shown all three BPs to be active. When compared with Cl(2)MBP, AHBuBP and AHHexBP wer e shown to be substantially active in inhibiting the release of beta-g lucuronidase from ionophore A23187-stimulated rat peritoneal M Phi.