Phagocytosis of codeveloping megakaryocytic progenitors by dendritic cells in culture with thrombopoietin and tumor necrosis factor-α and its possible role in hemophagocytic syndrome

Abstract

Tumor necrosis factor-alpha (TNF-alpha) and thrombopoietin (TPO) have been shown to induce the differentiation and proliferation of CD34+ cells toward dendritic cells (DCs) in the presence of multiacting cytokines. We hypothesized that the costimulation of TPO and TNF-alpha generates megakaryocytic progenitors and DCs together from human CD34+ cells and that the interaction of these cells may indicate a physiologic and/or a pathologic role of DCs in megakaryopoiesis. When highly purified human CD34+ cells were cultured for 7 days with TPO alone, the generated cells expressed megakaryocytic markers, such as CD41, CD42b, and CD61. The addition of TNF-alpha with TPO remarkably decreased the number of megakaryocytic progenitor cells without affecting the cell yield. Almost half of the cells thus generated expressed CD11c, and most of them were positive for CD4 and CD123. Furthermore, CD11c+ cells were found to capture damaged CD61+ cells and to induce autologous T-cell proliferation, although the cytokine productions were low. We also confirmed an engulfment of CD61+ cells and their fragment by CD11c+ cells in bone marrow cells from patients with hemophagocytic syndrome. These findings suggest that DCs generated under megakaryocytic and inflammatory stimuli are involved in megakaryopoiesis and the subsequent immune responses to self-antigens.