Hematological disorders and human macrophages.

Abstract

We report the results of in vitro experiments and in vivo studies to explore the possibility whether macrophage function might influence on the prognosis of human leukemia. At first, we noticed a transient but remarkable monocytosis during recovery after intensive chemotherapy in peripheral blood of patients with acute leukemia. Such remarkable monocytosis was observed only when they achieved a complete hematological remission. This may reflect the recovery of normal hematopoiesis, in addition, monocytes might contribute to the reduction of residual leukemic cells. To explore such possibility, we took advantage of monocyte-derived macrophages (Mφ). Mφ, pretreated with IFN-γ or LPS, lysed human leukemic cells, HL-60 and K562. When Mφ were pretreated with IFN-γ and LPS simultaneously, they lysed much more leukemic cells. Furthermore, activated Mφ could induce lysis of leukemic cells separated from Mφ by a microporous membrane. As to the mechanism of leukemic cell lysis by activated Mφ, TNF was found to be at least an important effector molecule. It was also suggested that TNF and other labile factor(s) might be involved in the leukemic cell lysis. Next, we measured the concentration of various cytokines in the blood of leukemia patients before chemotherapy, at nadir, and on recovery phase. Among them, the concentration of IL-6 was high on recovery phase. G-CSF was high at early recovery phase in the blood of some patients. In the patients with high grade fever the concentration of G-CSF, M-CSF, and IFN-γ was high. Elevated concentration of IL-6 may contribute for early recovery of normal blood cells.Monocyte-derived Mφ of patients with leukemia, obtained during monocytosis, lysed HL-60 to a similar extent as control Mφ. The finding that activated human Mφ could lyse human leukemic cells suggests a role of Mφ in the eradication of leukemic cells in vivo and supports the possibility of clinical application of activated Mφ.