PubMed Health⌕ Search

Biomedical subjects

S Ellermann-Eriksen

Publications and source records attributed to S Ellermann-Eriksen.

28 records · Page 2Linked to original sources
PubMed1992

Cytotoxic effects of hexavalent chromium in cultured murine macrophages.

The in vitro effect of hexavalent chromium (CrVI) on mouse peritoneal macrophages was investigated. Our results demonstrate the existence of a threshold concentration of 2.5 microM of CrVI above which chromium affects the viability of macrophages in a concentration dependent manner. Morphological changes were seen with increasing concentrations of chromium. Evidence is presented that protein production (virus-induced interferon) in murine peritoneal macrophages was impaired by hexavalent chromium at low concentrations, while random migration and phagocytic activity were only affected at high concentrations of CrVI.

Animals↗
PubMed1989

Herpes simplex virus type 2 primes mouse macrophages for an early and genetically determined respiratory burst mediated by interferon-alpha/beta.

The influence of infection by herpes simplex virus type 2 (HSV-2) on the respiratory burst capacity of mouse macrophages was studied by luminol-dependent chemiluminescence with phorbol myristate acetate (PMA) as trigger. Peritoneal cells from virus-infected mice were strongly primed for a respiratory burst during the acute phase of the infection. By 12 h after infection the response had increased 40-fold over control values. Most of the response was elicited by mononuclear phagocytes. When resting peritoneal macrophages were infected with HSV-2 in vitro a maximal priming effect was seen with 2 x 10(6) p.f.u./ml of virus after 8 h, but a significant response was obtained after 4 h of infection; after 12 h incubation with virus the response declined to reach background levels at 24 h. Peritoneal cells from C57BL/6 mice which are relatively resistant to HSV-2 showed a higher respiratory burst capacity after infection than cells from more susceptible BALB/c mice. Incubation of macrophages with crude niurine interferon (IFN)-alpha/beta produced by macrophages or purified murine IFN-alpha, in concentrations comparable to those obtained early (2 to 5 h) after infection of macrophage cultures with HSV-2 also augmented the respiratory burst. Addition of an IFN-alpha/beta-specific antiserum to HSV-2-infected cultures almost completely removed the response. We therefore conclude that HSV-2 induces an early and genetically determined activation of macrophages, mediated in an autocrine manner by IFN-alpha/beta secreted by the macrophages early during infection.

Animals↗
PubMed1989

Differential sensitivity of macrophages from herpes simplex virus-resistant and -susceptible mice to respiratory burst priming by interferon-alpha/beta.

Herpes simplex virus primes mouse macrophages for a genetically determined respiratory burst mediated in an autocrine manner by interferon (IFN)-alpha/beta. We have analysed the effect of IFN-alpha/beta on the respiratory burst capacity of mouse peritoneal macrophages by luminol-dependent chemiluminescence using phorbol myristate acetate as trigger. Crude macrophage-produced IFN-alpha/beta as well as purified IFN-alpha and -beta regularly augmented the respiratory burst capacity of peritoneal cells in a concentration-dependent manner. The augmented response was exclusively mediated by macrophages and was manifest after 4 h incubation with IFN-alpha/beta, peaked after 8 h and gradually declined to near background levels after 24 h. The effect of macrophage-produced IFN-alpha/beta was completely abolished by preincubation of IFN with antiserum to IFN-alpha/beta. The data obtained with this antiserum indicated that endogenous IFN, undetectable by a standard cytopathic effect-inhibition assay, was sometimes spontaneously produced by the peritoneal cells. Furthermore, the crude macrophage preparation seemed to contain a macrophage deactivating factor counteracting the effect of IFN-alpha/beta. Genetic analysis of the sensitivity of macrophages for the respiratory burst-priming effect of IFN-alpha/beta revealed that the trait is inherited as a co-dominant autosomal feature. Macrophages from herpes simplex virus-resistant C57BL/6 mice were more sensitive than macrophages from virus-susceptible BALB/c mice and cells from mice of the reciprocal crosses showed an equal sensitivity intermediate between those of the parental strains. A physiological role of differential IFN sensitivity in the context of resistance to virus infections is suggested.

Animals↗
PubMed1987

Effects of selenium on toxicity and ultrastructural localization of silver in cultured macrophages.

The effects of selenium on cellular toxicity and histochemical distribution of silver were examined in a cell culture system of mouse peritoneal macrophages. Selenium caused a significant delay in the appearance of coagulation necrosis induced by high silver concentrations and reduced the cytostatic effect of lower doses of silver when long-term toxicity was examined. Furthermore, selenium increased the amount of silver that could be visualized by autometallography. The additional silver made available for this histochemical demonstration was located in the cytosol as well as in lysosomes, the sole localization of silver when selenium was not administered.

Animals↗
PubMed1987

Autointerference in silver accumulation in macrophages without affecting phagocytic, migratory or interferon-producing capacity.

Silver accumulation and processing in mouse peritoneal macrophages was studied in vitro by autometallographic visualization of intracellular silver. During the first 24 h of incubation in a medium containing from 5 microM to 20 microM of silver lactate, an inverse relationship between silver concentration in the former and visualizable silver in macrophages was recorded. Later, however, the cells treated with higher silver concentrations accumulated most silver. Cells exposed to silver concentrations above these levels exhibited acute coagulation necrosis and disintegrated within the first 15 min of silver treatment. Macrophages treated with silver lactate concentrations not causing acute cytotoxicity showed no impairment of their phagocytic, migratory or interferon-producing capacities. The significance of autointerference in silver accumulation and processing in macrophages is discussed, and a functional defect in the lysosome/phagosome system is suggested as a basis for the phenomenon.

Animals↗
PubMed1986

X-linkage of the early in vitro alpha/beta interferon response of mouse peritoneal macrophages to herpes simplex virus type 2.

The genetics of the early interferon response of mouse peritoneal cells to infection with herpes simplex virus type 2 (HSV-2) was studied in susceptible BALB/c and more resistant C57BL/6 mice and in reciprocal crosses between these mice. Wash-outs of the peritoneal cavity of normal C57BL/6 mice contained significantly more cells than wash-outs from BALB/c mice. Therefore, interferon induction with HSV-2 was studied under standardized conditions in vitro. Peritoneal cells reacted to HSV-2 infection by interferon production in a virus dose-dependent manner. Interferon was detected first after 2 h and peaked after 24 h. Cells from C57BL/6 mice of each sex produced significantly more early interferon than cells from BALB/c mice, and cells from female BALB/c mice produced more interferon than cells from males. This difference was not seen with C57BL/6 mice. Cultures of highly purified adherent cells yielded approximately 10 times as much interferon as cultures of non-adherent cells. Since treatment of cells with carbonyl iron and silica significantly reduced the amount of interferon produced, whereas 2000 rad of irradiation had no obvious effect, it is concluded that the main interferon-producing cell in the peritoneal cavity of mice in response to HSV-2 is of the monocyte/macrophage lineage. Interferon production in peritoneal cells was found to be quantitatively influenced by X-linked loci in that cells from male (BALB/c female X C57 male) F1 mice, which inherit the X chromosome from the low-responding BALB/c females, produced significantly lower amounts of interferon than cells from the other three F1 generation genotypes. All interferons were characterized as alpha/beta interferon. It is suggested that the early production of alpha/beta interferon in response to HSV-2 is influenced by X-linked loci, which might be involved in sex-linked differences in resistance to human herpesviruses.

Animals↗
PubMed1986

Genetically determined difference in the antiviral action of alpha/beta interferon in cells from mice resistant or susceptible to herpes simplex virus type 2.

Resistance of mice to infection with herpes simplex virus type 2 (HSV-2) is genetically determined. Embryonic cells from susceptible BALB/c and resistant C57BL/6 mice were equally sensitive to infection with HSV-2 as judged by plaque area, plaquing efficiency, endpoint titration and virus yield. Cells from C57BL/6 mice showed a higher sensitivity than cells from BALB/c mice to the protective action of two preparations of alpha/beta interferon against challenge with HSV-2. This was evident both from c.p.e. inhibition and yield reduction experiments. The difference in sensitivity was dependent on virus dose and was greatest (up to 50-fold) with low virus doses. An analysis of the genetics of the alpha/beta interferon sensitivity in cells from embryos of parental mice and embryos derived from reciprocal matings between HSV-2-resistant and -susceptible mice suggested that interferon sensitivity is inherited as a co-dominant autosomal trait. The induction of the interferon-induced enzyme 2'-5'-oligoadenylate synthetase was also different in cells from the two mouse strains, since significant levels were only detected in cells from C57BL/6 mice. It is suggested that differential interferon sensitivity of cells from HSV-2-resistant and -susceptible mice might be a factor of importance for the course of the infection.

2',5'-Oligoadenylate Synthetase↗
PubMedDate not supplied

Interferon (IFN)-gamma and Herpes simplex virus/tumor necrosis factor-alpha synergistically induce nitric oxide synthase 2 in macrophages through cooperative action of nuclear factor-kappa B and IFN regulatory factor-1.

The radical nitric oxide (NO) constitutes an important part of the innate immune response to many viruses, and among these notably Herpes simplex virus (HSV). We have previously shown that HSV/tumor necrosis factor-alpha (TNF-alpha) and IFN-gamma synergistically induce NO production in macrophages, and here we have investigated the molecular mechanism underlying this phenomenon. The enhancement of NO production was regulated at the level of NO synthase 2 (NOS2, iNOS) transcription. The ISRE element of the NOS2 promoter, which binds IFN regulatory factor (IRF)-1, was essential both for full responsiveness to IFN-gamma and the synergistic response. The GAS motif, binding signal transducer and activator of transcription 1 (STAT1), did not contribute to the cross-talk with virus/TNF-induced signals, but was necessary for full responsiveness to IFN-gamma. The distal binding site for nuclear factor (NF)-kappa B was important for the cooperative response, while the proximal kappa B site was not involved in the cooperative promoter activation but played a role in full promoter inducibility. By ectopic expression of IRF-1 and NF-kappa B (p65), we found that these factors synergistically induce NO accumulation. Together, our results show that binding of IRF-1 and NF-kappa B to their respective sites in the distal domain of the NOS2 promoter, creates a potent trans-activating complex with the ability to induce NOS2 transcription synergistically in response to simultaneous HSV-2/TNF-alpha and IFN-gamma treatment.

Animals↗