Phosphatidylinositol 3‐kinase and extracellular signal‐regulated kinase are recruited for Fc receptor‐mediated phagocytosis during monocyte‐to‐macrophage differentiation

The molecular mechanism involved in Fc receptor‐mediated phagocytosis in the different cell types of the immune system is still poorly defined. We investigated the role of phosphatidylinositol 3‐kinase (PI 3‐K) and extracellular signal‐regulated kinase (ERK) in phagocytosis by monocytes and by monocyte‐differentiated macrophages. Peripheral blood monocytes and monocytic cells (THP‐1 cell line) were able to ingest IgG‐coated erythrocytes in the absence of additional stimulus. Phagocytosis by these cells was not blocked by wortmannin and LY294002, specific inhibitors of PI 3‐K, or by PD98059, a specific MEK/ERK inhibitor. However, upon differentiation of THP‐1 monocytes to macrophages, through treatment with retinoic acid and interferon‐γ (IFN‐γ), wortmannin and PD98059 blocked Fc receptor‐mediated phagocytosis efficiently. Inhibition of phagocytosis by PD98059 was observed after 24 h of IFN‐γ treatment, whereas wortmannin could inhibit phagocytosis only after 48 h of IFN‐γ treatment. Additionally, phagocytosis of IgG‐coated erythrocytes by neutrophils, a more efficient phagocyte, was inhibited by wortmannin and PD98059. Neutrophils and monocyte‐differentiated macrophages presented significantly more efficient phagocytosis than monocytes upon PMA stimulation. Taken together, these results indicate that poorly phagocytic leukocytes, such as monocytes, do not require PI 3‐K and ERK for phagocytosis. Upon differentiation into macrophages, however, ERK first and PI 3‐K second are recruited for regulation of phagocytosis. In addition, our data support the idea that professional phagocytes require ERK and PI 3‐K for efficient phagocytosis.