Abstract
We demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage-CSF (M-CSF) stimulate the differentiation of CD14+ human monocytes into two phenotypically distinct types of macrophages, based on morphorogy, cell surface antigen expression and functions including phagocytosis, production of reactive oxygen intermediate, antigen presenting activity and sensitivity to HIV infection. In vivo, however, not only CSF but also many other cytokines are produced under various conditions, and those cytokines may modulate the differentiation of monocytes by CSFs. We demonstrated that CD14+ human monocytes can differentiate into CD1+ re1B+ dendritic cells (DC) by combination of GM-CSF plus interleukin-4 (IL-4), and that they differentiate into tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like multinucleated giant cells (MGC) by combination of M-CSF plus IL-4. However, the monocyte-derived DC were not terminally differentiated cells; they could still convert to macrophages in response to M-CSF. Tumor necrosis factor-α (TNF-α) stimulated the terminal differentiation of the DC by down-regulating the expression of the M-CSF receptor, c-fms mRNA and aborting the potential to convert to macrophages. Taken together, these results provide a new aspect to our knowledge of monocyte differentiation, providing evidence that human monocytes are flexible in their differentiation potential, and that they are precursors not only of macrophages but also of CD1+ re1B+ DC and TRAP-positive MGC. Such a diverse pathway of monocyte differentiation may constitute one of the basic mechanisms of immune regulation.
