Differentiation, apoptosis, and function of human immature and mature myeloid cells: intracellular signaling mechanism.

Abstract

Human myeloid cells include hematopoietic cells at various stages of differentiation, from immature myeloid cells to mature phagocytes. Normal immature myeloid cells undergo differentiation concomitantly with proliferation in response to hematopoietic growth factors, and terminally differentiated cells, ie, mature phagocytes, exert their effector functions and then die a natural death via apoptosis. However, leukemic myeloid cells are induced to differentiate with growth suppression by several inducers, such as retinoic acid. This review describes differentiation, apoptosis, and functionality of human myeloid cells. mainly focusing on the intracellular signaling mechanism. The signal transduction system for these biological events of the life cycle of myeloid cells has recently been studied, and several characteristics have been elucidated. First, the signaling pathway for myeloid differentiation is mainly focused in the mitogen-activated protein kinases, such as extracellular signal-regulated kinase and p38, and transcriptional factors such as the signal transducers and activators of transcription PU.1 and CCAAT enhancer binding protein. Second, the signaling mechanism for myeloid cell apoptosis is fundamentally identical to that found in other cells. Caspases, caspase-activated DNase, and mitochondrial molecules such as apoptosis-inducing factor have been reported to be important, and mitogen-activated protein kinases such as p38 appear to be less important. Finally, p38 and phosphatidylinositol 3-kinase play critical roles in the signaling cascade for functional activation of mature phagocytes. The reasons why the same signaling molecules play distinct roles according to the differentiation stage and biological event await future clarification.