Effects of bisphosphonate derivatives on macrophage function

The effects of three bisphosphonates (BPs), designated 4-amino-1-hydroxybutylidene-1, 1-bisphosphonate (AHBuBP), 6-amino-1-hydroxylidene-1, 1-bisphosphonate (AHHexBP) and chloromethylenebisphosphonate (Cl2MBP), were evaluated on the basis of their effect on the phagocytic activity, lysosomal enzyme release and superoxide anion production in the rat peritoneal macrophage (M phi). AHBuBP was found to inhibit in a concentration-dependent manner the phagocytosis of sheep red blood cells (SRBC). The same activity was seen with the phagocytosis of latex beads, although this effect was independent of calcium concentration. Conversely, AHHexBP and Cl2MBP were weak inhibitors of phagocytosis of both 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 Cl2MBP, AHBuBP and AHHexBP were shown to be substantially active in inhibiting the release of beta-glucuronidase from ionophore A23187-stimulated rat peritoneal M phi.