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.

CMVpp65 Vaccine Enhances the Antitumor Efficacy of Adoptively Transferred CD19-Redirected CMV-Specific T Cells

“…Interestingly, mice that received bi-specific T cell treatment had to be euthanized around the same time as control mice even though the tumor signals were dramatically lower (Figure 5). Our further studies indicated that there were highly elevated levels of human specific IFNγ and IL-6 in the mouse serum (Supplemental Figure S3) and it is probable that the mice died of cytokine release syndrome (25) rather than tumor. More interestingly, augmented anti-tumor efficacy induced by pp65 vaccine was supported in a relapsed tumor model (Supplemental Figure S4).…”

IFN-ε protects primary macrophages against HIV infection

“…Immune activation has been shown to enhance phagocytosis and induce production of ROS, which play an important role in control of infection (41)(42)(43)(44)(45)(46)(47). Transcriptome analysis indicated that IFN-ε but not IFN-α induced the expression of genes involved in phagocytosis and ROS production ( Figure 6A).…”

Interferon-gamma enhances phagocytosis, the production of reactive oxygen species and pro-inflammatory cytokines – implications for innate and acquired immunity.

“…IFN-γ has recently been produced by recombinant DNA techniques, providing a new opportunity to characterize the immunomodulatory properties this cytokine [4] . In our recent study titled "In vitro activation of mouse neutrophils by recombinant human interferon-gamma: increased phagocytosis and release of reactive oxygen species and pro-inflammatory cytokines" [5] , we investigate the ability of IFN-γ to modulated the functions of mouse neutrophils in vitro.…”

“…Our research group has being greatly interested in understanding the role of neutrophils in the interplay between the innate and acquired immune responses [5,7,8,9,10,11] , addressing the functional similarities and differences with macrophages. It has been suggested that during inflammation or specific immune responses, mature myeloid cells may respond to humoral factors in a manner analogous to macrophages [12] .…”