title: Interferon gamma induces actin polymerization, Rac1 activation and down regulates phagocytosis in human monocytic cells.
abstract: IFNγ is a potent activator and IL-10 a powerful inhibitor of macrophage functions. However, neither all cellular functions are enhanced by IFNγ nor IL-10 inhibits all cellular responses. Thus, FcγRs-mediated phagocytosis in monocyte-derived macrophages (MDM) increases after IL-10 treatment, and decreases after treatment with IFNγ, although both IL-10 and IFNγ up regulate FcγRI expression. In this work we investigated the effect of IFNγ and IL-10 on phagocytic signaling by FcγRs in MDM. Treatment with IFNγ diminished phagocytosis of IgG-opsonized SRBC (IgG-SRBC) while treatment with IL-10 increased it. These opposite effects cannot be attributed to changes in FcγR expression induced by each cytokine. Early biochemical responses mediated by FcγRs were distinctly affected by cytokine treatment. Syk phosphorylation and the rise in [Ca(2+)](i) were higher after IL-10 treatment, whereas IFNγ treatment also increased Syk phosphorylation but had no effect on the rise in [Ca(2+)](i). IFNγ treatment led to increased basal levels of F-actin and this effect correlated with the decrease in phagocytosis of both IgG-SRBC and non-opsonized Escherichia coli. IL-10 did not alter F-actin basal levels, and enhanced the phagocytosis of E. coli and IgG-SRBC. The level of F-actin reached after IFNγ treatment was not further increased after stimulation with IgG-SRBC or CCL5, whereas MDM treated with IL-10 showed a slightly higher response than control cells to CCL5. IFNγ increased Rac1-GTP levels. Inhibition of PI3K with LY294002 prevented IFNγ-mediated actin polymerization. Our data suggest that IFNγ induces a higher basal level of F-actin and activation of Rac1, affecting the response to stimuli that induce cytoskeleton rearrangement such as phagocytic or chemotactic stimuli.
authors.affiliation: Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Apartado Postal 70228, Ciudad Universitaria, DF 04510, Mexico.
authors.forename: Dulce
authors.initials: D
authors.lastname: Frausto-Del-Río
authors.forename: Isabel
authors.initials: I
authors.lastname: Soto-Cruz
authors.forename: Claudia
authors.initials: C
authors.lastname: Garay-Canales
authors.forename: Xochitl
authors.initials: X
authors.lastname: Ambriz
authors.forename: Gloria
authors.initials: G
authors.lastname: Soldevila
authors.forename: Jorge
authors.initials: J
authors.lastname: Carretero-Ortega
authors.forename: José
authors.initials: J
authors.lastname: Vázquez-Prado
authors.forename: Enrique
authors.initials: E
authors.lastname: Ortega
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D018946:Chemokine CCL5 / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D004926:Escherichia coli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D016753:Interleukin-10 / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects; D009895:Opsonin Proteins / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D058105:Polymerization / Q000187:drug effects*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D012756:Sheep; D000072377:Syk Kinase; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000199:Actins; D018946:Chemokine CCL5; D003432:Cross-Linking Reagents; D007074:Immunoglobulin G; D007371:Interferon-gamma; D016753:Interleukin-10; D047908:Intracellular Signaling Peptides and Proteins; D009895:Opsonin Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D017452:Receptors, IgG; D000072377:Syk Kinase; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; C483024:CCL5 protein, human; C000606896:SYK protein, human