The mononuclear phagocyte system (MPS) exemplifies cells differentiation generating functional and phenotypic diversity. Cells of the MPS origin from bone marrow hematopoietic stem cells differentiating through progenitor intermediates to monocytes, which enter circulation, migrate into tissue and terminally differentiate to replenish resident dendritic cells and macrophages. Macrophages differ from their monocytic precursors morphologically and functionally. Monocytes and macrophages are both critical effectors and regulators of inflammation and the innate immune response e.g., by producing growth factors and cytokines. The phenotypic and functional diversity of MPS cells depends on differentiating programs being strictly related to local environmental factors. Recent interest was deserved to the signal transduction pathways acting in macrophage polarization, including the phosphoinositide (PI) system and related phospholipase C (PLC) family of enzymes. PLCs are strictly tissue specific and the expression panel, as well as the subcellular localization differs in quiescent cells compared to the pathological counterpart. Our previous work demonstrated the involvement of PLC enzymes during differentiation of macrophages from unpolarized (M0) into M1 and M2. Human leukemia model cell lines with monocytic characteristics such as the human cell line THP-1, frequently used as a model system with monocytic properties. THP-1 cells can be differentiated into macrophage-like cells that resemble properties of mature macrophages by activation of protein kinase C (PKC) with phorbol-12-myristate-13-acetate (PMA), resulting in cells with increased adherence and loss of proliferative activity. In the present project we aim to investigate the differentiation of THP-1 cells. Once differentiated, we want to investigate: 1) the involvement of PI signaling, 2) the production of cytokines and 3) the effects of the tumour environment.
