Modulation of murine macrophage responses stimulated with influenza glycoproteins

Abstract

Previously it was reported that influenza virus stimulated, nonspecific resistance was largely due to its glycoproteins, hemagglutinin (HA) and neuraminidase (NA). The enhancement of natural killer cell activity was the intrinsic property of NA and HA. In the present study, the stimulatory effect of these glycoproteins on the murine peritoneal macrophages was studied. Electrophoretically purified glycoproteins, NA and HA, of influenza virus A/USSR/90/77 (H1N1) were administered intraperitoneally to C3H/HeN mice, with or without stearyl tyrosine (ST). Macrophages were isolated and were restimulated with phorbol myristate acetate. H2O2 secretion was determined by horseradish peroxidase dependent oxidation of phenol red assay. HA enhanced H2O2 secretion only in the presence of ST (60 nmol.mg-1.h-1), whereas NA alone stimulated H2O2 secretion (83 nmol.mg-1.h-1), by 6-fold over control (13 nmol.mg-1.h-1), and this stimulation was further increased (136 nmol.mg-1.h-1) in the presence of ST. Interleukin 1 (IL-1) activity was determined by using D10.G4.1 cells. There was a little stimulation of IL-1 activity (less than 1 U/mL) of macrophages isolated from HA-primed of HA+ST-primed mice restimulated with HA. On the other hand, IL-1 activity of macrophages isolated from NA-primed mice restimulated with NA significantly increased (102 U/mL) over control (less than 1 U/mL), and an additional 2-fold increase (231 U/mL) resulted when macrophages from NA+ST-primed mice were used. Tumor necrosis factor (TNF) activity was examined by using L929 cells. Negligible TNF activity was observed in macrophages isolated from either HA-primed or HA+ST-primed mice restimulated with HA.(ABSTRACT TRUNCATED AT 250 WORDS)

A Fungal Cu/Zn-Containing Superoxide Dismutase Enhances the Therapeutic Efficacy of a Plant Polyphenol Extract in Experimental Influenza Virus Infection

“…They have a part in pulmonary tissue damage, hypoxia, and toxicosis due to their toxic properties; on the other hand, they can induce apoptosis in virus-infected cells, thus contributing to the decrease in the total viral load. In this way ROS offer the fi rst line of defense against infection, preceding the alternative defense mechanisms of the organism (Arora and Houde, 1992). The presented results together with our previous data (Murzakhmetova et al, 2008) show that infl uenza A/Aichi virus infection is accompanied with defi cits in antioxidant enzyme activities and an increase in ROS and lipid peroxidation (LPO) levels in the lungs, livers, and sera, which can be overcome through supplementation with antioxidants.…”

Global Host Immune Response: Pathogenesis and Transcriptional Profiling of Type A Influenza Viruses Expressing the Hemagglutinin and Neuraminidase Genes from the 1918 Pandemic Virus

“…It is conceivable that the combination of high levels of TNF expression and the inhibition of NF-B activation (inferred from upregulated Nfkbia expression) act synergistically to cause signifi- 54). Specifically, the generation of oxygen radicals has been shown to be an important aspect of influenza virus virulence and pathology (3,6,13,14,20,50,79). Accordingly, we have identified the up-regulation of several important genes involved in the production of and response to superoxide radicals in the lungs of mice infected with influenza viruses.…”

Molecular Pathways in Virus-Induced Cytokine Production

“…It was further shown that the IFN-inducing potential of a specific strain correlated with the NA activity. Houde and Arora showed that recombinant NA, but not HA, induced the production of IL-1 and TNF-␣ in murine peritoneal macrophages (9,104,105), and another study has shown that NA promotes the conversion of TGF-␤ from the latent to the active form to an extent sufficient to induce TGF-␤-dependent apoptosis (223). The exact mechanism through which NA induces cytokine expression remains obscure yet is very important, given the high immunostimulatory activity of this viral protein.…”