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-gamma (IFN-gamma), wortmannin and PD98059 blocked Fc receptor-mediated phagocytosis efficiently. Inhibition of phagocytosis by PD98059 was observed after 24 h of IFN-gamma treatment, whereas wortmannin could inhibit phagocytosis only after 48 h of IFN-gamma 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.
García-García
Erick
E
Department of Immunology, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Cd. Universitaria, Mexico City, Mexico D.F.-04510.
Rosales
Ricardo
R
Rosales
Carlos
C
D002454:Cell Differentiation; D002460:Cell Line; D006801:Humans; D008264:Macrophages / Q000201:enzymology / Q000276:immunology; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000201:enzymology / Q000276:immunology; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology; D010586:Phagocytes / Q000201:enzymology* / Q000276:immunology; D010587:Phagocytosis; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D012333:RNA, Messenger / Q000096:biosynthesis; D011961:Receptors, Fc / Q000502:physiology*
D012333:RNA, Messenger; D011961:Receptors, Fc; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases