title: In vitro activation of mouse neutrophils by recombinant human interferon-gamma: increased phagocytosis and release of reactive oxygen species and pro-inflammatory cytokines.
abstract: Here, we investigated the ability of IFN-γ to modulate the functions of mouse neutrophils in vitro. Neutrophils incubated in the presence of IFN-γ showed enhanced phagocytosis in response to zymosan, opsonized zymosan or precipitated immune complexes of IgG and ovalbumin. The effect of IFN-γ was dose-dependent with an initial response at 10 U/ml and a maximal response at 150 U/ml; 2 h of incubation were required to reach the optimal response level. These stimuli can also induce IFN-γ-pretreated neutrophils to release reactive oxygen species (ROS), such as superoxide anion, hydrogen peroxide and hypochlorous acid, as well as granule lysosomal enzymes and the pro-inflammatory cytokines TNF-α and IL-6. We found that increased expression of FcγR, dectin-1 and complement receptors (CRs) correlated with these effects in these cells. The enhancing effect of IFN-γ on the respiratory burst was found to be associated with up-regulation of the gp91(phox) and p47(phox) subunits of NADPH oxidase, as measured by their mRNA levels. The enhancing effect of IFN-γ on phagocytosis and ROS release may not only be relevant for the efficient killing of invading microorganisms, but may also produce oxidative stress on adjacent cells, resulting in a possible inflammatory role that could also be favored by the liberation of the pro-inflammatory cytokines TNF-α and IL-6.
authors.affiliation: Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes, 3900, Monte Alegre, 14049-900 Ribeirão Preto, SP, Brazil. Electronic address: larissafavaromarchi@gmail.com.
authors.forename: L F
authors.initials: LF
authors.lastname: Marchi
authors.affiliation: Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes, 3900, Monte Alegre, 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Sesti-Costa
authors.affiliation: Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes, 3900, Monte Alegre, 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: M D C
authors.initials: MD
authors.lastname: Ignacchiti
authors.affiliation: Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes, 3900, Monte Alegre, 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: S
authors.initials: S
authors.lastname: Chedraoui-Silva
authors.affiliation: Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes, 3900, Monte Alegre, 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: B
authors.initials: B
authors.lastname: Mantovani
mesh_terms: D000818:Animals; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D037181:Lectins, C-Type / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D000099181:Dectin-1
chemical_list: D007371:Interferon-gamma; D037181:Lectins, C-Type; D016177:Macrophage-1 Antigen; D017382:Reactive Oxygen Species; D017452:Receptors, IgG; D011994:Recombinant Proteins; D000099181:Dectin-1; C573415:IFNG protein, human
keywords: Immune complex; Interferon-γ; NADPH oxidase; Neutrophil; Phagocytosis; Reactive oxygen species