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

Abstract

In order to explore the effect on bone marrow macrophages of liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP), mice were injected intravenously with a preparation of such liposomes at a dose known to deplete spleen and liver macrophages. Two days later, the macrophages in the marrow of the femoral bones were quantified by flow cytometry using a macrophage-specific 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 marrow macrophages, red blood cell parameters and the formation of erythroid burst-forming unit (BFU-E)-derived colonies in vitro were evaluated. In mice injected with liposome-encapsulated Cl2MDP, there was a 54% and 67% decrease in the total number of bone marrow macrophages as compared to uninjected controls and mice treated with empty liposomes, respectively. Moreover, residual macrophages showed an abnormal ultrastructure, with reduced numbers of crystalloid inclusions and increased numbers of large myelin figures. However, the phagocytic activity of these cells was unimpaired or slightly enhanced. In mice injected with liposome-encapsulated Cl2MDP there was an approximately 60% decrease in the percentage and total number of circulating reticulocytes and a 54% reduction in the BFU-E number, demonstrating deregulation of erythropoiesis under conditions of macrophage loss and impairment. The results suggest that mice treated with liposome-encapsulated Cl2MDP are a model for studying the role of macrophages in erythropoiesis.

Macrophage depletion following liposomal‐encapsulated clodronate (LIP‐CLOD) injection enhances megakaryocytopoietic and thrombopoietic activities in mice

“…injection of LIP‐CLOD 19 µg and 76 µg/mouse, the total number of macrophages in femoral bone marrow was significantly reduced by 25% and 50% respectively. This result is consistent with the immunohistochemical and flow cytometry findings reported by others (Endo et al , 1995; Giuliani et al, 2001).…”

Preconditioning with Hemin Decreases Plasmodium chabaudi adami Parasitemia and Inhibits Erythropoiesis in BALB/c Mice

“…Considering that macrophages play important roles in erythropoiesis [31], we evaluated the impact of hemin on the population of resident macrophages (F4/80 + cells) in the bone marrow, and no significant effect was revealed with the dose of hemin tested (Fig. 2E).…”

“…The importance of macrophages in erythropoiesis has been underscored by the fact that treatment with liposome-encapsulated dichloromethylene biphosphonate depletes femoral macrophages and results in inefficient generation of blast forming erythroid units (BFU-E) ex-vivo [31]. Although administration of hemin during 3 consecutive days failed in altering the numbers of bone marrow macrophages, treatment with hemin for an additional week decreased significantly the numbers of macrophages in the femoral bone marrow (Figure S1).…”

Accelerated Tumor Progression in Mice Lacking the ATP Receptor P2X7

“…Isolation of bone marrow-derived DCs and peritoneal macrophages from wt and P2X7R-KO mice Bone marrow cells were obtained as previously described (18,19). Tibiae and femurs from 6-week-old mice were removed, cut, and the marrow flushed with RPMI.…”