Macrophage depletion following liposomal-encapsulated clodronate (LIP-CLOD)

ALVES-ROSA F, VERMEULEN M, CABRERA J, STANGANELLI C, CAPOZZO A, NARBAITZ M, VAN

Br J Haematol

Lugar: London; Año: 2003 vol. 121 p. 130 - 138

Megakaryocytopoiesis is the cellular process by which stem cells progress throughcommitment, proliferation and differentiation, leading to the production ofplatelets. In the mouse, this process is accomplished within the bone marrow (BM)and spleen microenvironment and is carried out by regulatory molecules andaccessory cells, including macrophages, fibroblasts and endothelial-like cells.Previously, we demonstrated that specific macrophage depletion, usingliposomal-encapsulated clodronate (LIP-CLOD), induced a rapid recovery of theplatelet count in a mouse model of immune thrombocytopenia. We now show thatLIP-CLOD treatment also provoked enhancement of both megakaryocytopoiesis andthrombocytopoiesis. In fact, a dose-dependent increase in the number of BM andspleen megakaryocytes was detected after treatment and this pattern correlatedinversely to the macrophage count detected in these organs. Furthermore, the micetreated with the higher dose of LIP-CLOD showed signs of enhanced thrombopoiesis as they had an increased frequency of reticulated platelets and an improvement inthe total platelet count 2 d later. In addition, the in vitro cytokine-inducedmegakaryocytopoiesis in BM and spleen cell cultures was significantly augmentedin the presence of LIP-CLOD. Taken together, these results suggest that BM andspleen microenvironmental macrophages could be involved in the regulation ofmegakaryocyte and platelet production.