Conversion of the U937 Monocyte into "Macrophage-Like" Populations Exhibiting M1 or M2 Characteristics

The U937 cell line is an oncogenic human monocyte cell line. These monocytes have the potential of differentiating into either macrophages or dendritic cells (Lawrence et al., 2011). This differentiation pattern depends on the characteristics of the tissue microenvironment (Kigerl et al., 2009). PMA (Phorbol 12-Myristate 13-Acetate) is a phorbol ester capable of transforming monocytic cells toward the macrophage pathway. Upon treatment with PMA, U937 cells under-go a series of morphological and functional changes. Traditionally monocytic cell lines are used as a model of macrophage function, because current human macrophage cell lines require a T-cell conditioned growth medium and contact with irradiated peripheral blood leukocytes (PBLs) to propagate (Lee et al., 1997). The PMA-treated monocyte is referred to as "macrophage-like," meaning that the properties of the transformed cell line are not yet fully understood (Dockrell et al., 2010). These macrophages are clinically significant for possible cancer immunotherapy experimentation. Recently, two divergent macrophage subsets have been identified: M1 (pro-inflammatory) and M2 (anti-inflammatory). These macrophages are differentiated based on the cytokines present in the extracellular matrix (Kigerl et al., 2009). In order for the U937 cell line to be represented as an effective macrophage model, the ability of the cell line to polarize must be analyzed. This study is a review of the features necessary to convert the human U937 cell line into M1 or M2 morphological and functional subsets.