Changes in murine bone marrow macrophages and erythroid burst-forming cells following the intravenous injection of liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP)

In order to explore the effect on bone marrow macrophages of liposome-encap sulated dichloromethylene diphosphonate (Cl2MDP), mice were injected intrav enously with a preparation of such liposomes at a dose known to deplete spl een and liver macrophages. Two days later, the macrophages in the marrow of the femoral bones were quantified by flow cytometry using a macrophage-spe cific monoclonal antibody (F4/80), and their ultrastructure and phagocytic activity towards zymosan particles was assessed. To determine the effect on erythropoiesis of liposome-encapsulated Cl2MDP-induced changes in bone mar row macrophages, red blood cell parameters and the formation of erythroid b urst-forming unit (BFU-E)-derived colonies in vitro were evaluated. In mice injected with liposome-encapsulated Cl2MDP, there was a 54% and 67%, decre ase in the total number of bone marrow macrophages as compared to uninjecte d controls and mice treated with empty liposomes, respectively. Moreover, r esidual macrophages showed an abnormal ultrastructure, with reduced numbers of crystalloid inclusions and increased numbers of large myelin figures. H owever, the phagocytic activity of these cells was unimpaired or slightly e nhanced. In mice injected with liposome-encapsulated Cl2MDP there was an ap proximately 60% decrease in the percentage and total number of circulating reticulocytes and a 54% reduction in the BFU-E number, demonstrating deregu lation of erythropoiesis under conditions of macrophage loss and impairment , The results suggest that mice treated with liposome-encapsulated Cl2MDP a re a model for studying the role of macrophages in erythropoiesis.