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Biomedical subjects

O Haller

Publications and source records attributed to O Haller.

At least 109 records · Page 6Linked to original sources
PubMed1979

Natural, genetically determined resistance toward influenza virus in hemopoietic mouse chimeras. Role of mononuclear phagocytes.

Radiation chimeras produced by crosswise transfers of bone-marrow cell among histocompatible mice susceptible, or genetically resistant, to lethal challenge by a number of myxoviruses were used to test whether macrophage resistance (as assessed in vitro) and resistance of the animal (as measured in vivo), both previously shown to be brought about by the gene Mx, were causally related. 49 chimeras were tested individually, both of resistance of their macrophages to in vitro challenge with M-TUR (a strain of avian influenza virus A/Turkey/England/63 adapted to grow in cultured mouse peritoneal macrophages), and for resistance of the animal in vivo upon challenge with pneumotropic, neurotropic, or hepatotropic influenza viruses. Cultivated Kupffer cells and peritoneal macrophages harvested from chimeric mice expressed the resistance phenotype of the bone-marrow donor irrespective of the host environment in which they had differentiated. However, susceptibility or resistance in vivo was according to the genotype of the host. Thus, inborn resistance of radiation chimeras was found to be independent of Mx-gene expression in cells of the hemopoietic system.

Animals↗
PubMed1979

Genetically determined, interferon-dependent resistance to influenza virus in mice.

The genetically determined resistance towards orthomyxoviruses exhibited by mice homozygous (A2G) or heterozygous (A2G X A/J) for the gene Mx was abolished or greatly diminished by treatment with anti-interferon globulin (AIF). AIF induced increased susceptibility to challenge with hepatotropic, neurotropic, and pneumotropic strains of influenza A virus. Hepatotropic virus titers in blood and livers of AIF-treated, Mx-bearing mice were higher by a factor of 10(3)--10(6) than those in untreated mice of the same genotype, and were comparable to those in genetically susceptible (untreated or AIF-treated) mice. Peritoneal macrophages from Mx-bearing untreated mice were resistant to challenge with a macrophage-adapted strain of influenza A virus even in the presence of AIF. However, when macrophages were taken from resistant mice injected with AIF and also cultivated in the presence of AIF, they were as susceptible to the virus as macrophages taken from susceptible mice. We conclude that interferons is an important factor in resistance to orthomyxoviruses governed by the gene Mx.

Animals↗
PubMed1979

A functional comparison of tumor cell killing by activated macrophages and natural killer cells.

This report compares the sensitivity of 17 tumor cell lines to cytolysis mediated by natural killer (NK) cells or by activated, bone marrow-derived macrophages (AM) from 15 inbred mouse strains. Some tumor cell lines, notably P815, were highly sensitive to AM-mediated lysis but almost completely insensitive to NK cells, whereas other cell lines were lysed by NK cells but not AM. In a genotype survey, some low-responder strains in the NK system, such as A/Sn, were high responders in the AM system, and conversely, one intermediate to high-responder strain (C3H/HeJ) in the NK system was a low responder in AM-mediated cytolysis. In addition, macrophage cytotoxicity factor was necessary to activate macrophages, but this lymphokine did not augment NK activity. Furthermore, the NK population did not contain pre-activated macrophages since pre-activated cells were removed on glass bead columns or by iron carbonyl and a magnet; treatments which have been previously shown not to affect NK cells. These results suggest that NK cells are distinct from AM in physical characteristics, target selectivity, genotype distribution and the mechanism of cytolysis.

Animals↗
PubMed1979

Macrophage immunity to influenza virus: in vitro and in vivo studies.

Using M-TUR, a macrophage-adapted avian influenza A virus (Hav1, Nav3), antiviral resistance of peritoneal macrophages obtained from specifically or nonspecifically immunized mice towards in vitro infection was assessed. M-TUR grew to high titers in macrophages from nonimmune mice thereby causing a marked cytopathic effect. In contrast, peritoneal macrophages from mice specifically immunized with TUR virus were not affected by infection with M-TUR in vitro. This antiviral immunity was specific: mice immunized with antigenetically unrelated influenza strains such as influenza A/Hong Kong/1/68 (H3, N2) or influenza B/Lee yielded susceptible macrophages. Specific macrophage immunity could be abrogated by trypsin treatment in vitro. Susceptible macrophages from nonimmune hosts became resistant following in vitro exposure to homologous anti-TUR sera. Peritoneal exudate cells from BCG-infected animals were less susceptible to in vitro challenge with M-TUR than control macrophages. In vivo treatment of mice with the unspecific immunostimulants BCG or Corynebacterium parvum did not protect the animals against lethal infection with a hepatotropic variant of TUR.

Animals↗
PubMed1978

An analysis of conditions allowing Corynebacterium parvum to cause either augmentation or inhibition of natural killer cell activity against tumor cells in mice.

We have analyzed the impact of in vivo administration of Corynebacterium parvum on the mouse immune system against murine tumors, using the natural cytotoxic ability against tumors of normal mouse lymphoid cells as a baseline. A striking difference was found depending on the route of administration. Intravenous inoculation of bacteria would result in a significant decrease or sometimes complete abolition of natural cytotoxicity toward tumor cells of the spleen cells of treated mice. On the other hand, the intraperitoneal route of administration resulted in a dramatic increase in cytolytic ability of the peritoneal exudate cells. Both routes of treatment had the most significant impacts on the local cell population (IV = spleen, IP = peritoneal exudate cells) with only minor effects on other cell populations. Analysis of the spleen cell population from IV-treated mice did also demonstrate a significant reduction in the T lymphocyte function, but in contrast to the natural cytotoxicity this could be corrected for by the removal of suppressor cells of an adherent nature. The lytic cells induced in the peritoneal exudate by the Corynebacterium parvum bacteria were all found to be natural killer, NK, cells with no significant activity found amongst macrophages using short-term cytolytic assays.

Animals↗
PubMed1978

Mouse natural killer (NK) cell activity against human cell lines is not influenced by superinfection of the target cell with xenotropic murine C-type virus.

Mouse natural killer (NK) cells can lyse a variety of syngeneic, allogeneic and xenogeneic target cells in short-term 51Cr release assays. The target specificity of NK cells is not known, but endogenous C-type viral antigens have been suggested as possible target structures. To test this hypothesis, human lymphoid lines were superinfected with xenotropic mouse C-type virus either by repeated dosage through nude mice or by in vitro superinfection with the supernatants of nude-mouse-passaged lines. The appearance of surface-associated MuLV antigens after superinfection was confirmed in a complement-dependent cytotoxicity test. Subsequently, the NK sensitivity of each infected line was compared with its non-infected counterpart in direct cytolytic and competition assays. None of these two assay systems showed a consistent difference in NK sensitivity of infected and non-infected cell lines. These findings do not lend support to the concept tht murine C-type viral antigens are responsible for NK sensitivity.

Animals↗
PubMed1978

Inborn resistance of mice to myxoviruses: macrophages express phenotype in vitro.

A strain of avian influenza A virus was adapted to grow in mouse peritoneal macrophages in vitro. The adapted strain, called M-TUR, induced a marked cytopathic effect in macrophages from susceptible mice. Mice homozygous (A2G) or heterozygous (F1 hybrids between A2G and several susceptible strains) for the gene Mx, shown previously to induce a high level of resistance towards lethal challenge by a number of myxoviruses in vivo, yielded peritoneal macrophages which were not affected by M-TUR. Peritoneal macrophages could be classified as resistant or susceptible to M-TUR without sacrificing the cell donor. Backcrosses were arranged between (A2G X A/J)F1 and A/J mice. 64 backcross animals could be tested individually both for resistance of their macrophages in vitro after challenge with M-TUR, and for resistance of the whole animal in vivo after challenge with NWS (a neurotropic variant of human influenza A virus). Macrophages from 36 backcross mice were classified as susceptible, and all of these mice died after challenge. Macrophages from 28 mice were classified as resistant, and 26 mice survived challenge. We conclude that resistance of macrophages and resistance of the whole animal are two facets of the same phenomenon.

Alleles↗
PubMed1978

A new surface marker on mouse natural killer cells: receptors for Helix pomatia A hemagglutinin.

Natural killer (NK) cells in normal mouse spleen have so far been found to lack conventional cell surface markers. Recently, neuraminidase treatment has been shown to uncover receptors for the A hemagglutinin of the snail Helix pomatia (HP) on populations (preferentially T cells) of human blood lymphocytes. We have used HP coupled to Sepharose in columns to fractionate mouse spleen cells. Fractions consisted of passed cells (fraction I) and cells eluted with the competitive hapten N-acetyl-D-galactosamine at either 0.1 mg/ml (fraction II) or 1.0 mg/ml (fraction III), NK activity and percentage of T and B cells in each fraction were determined. B cells were found enriched in fraction I. T lymphocytes, among them alloreactive cytotoxic T cells (CTL), were eluted in fraction III. However, NK activity of normal CBA spleens was highest in fraction II, fraction III was somewhat enriched, whereas fraction I was depleted of lytic activity. Thus, while NK cells possess HP receptors, their binding properties seem to differ from those of CTL. HP receptors represent the first simple and reliable marker detected on NK cells and might be useful for purification of this cell type.

Agglutinins↗
PubMed1978

Mouse natural cell-mediated cytotoxicity to human leukemia: independence of serum source used for target-cell culturing and cytotoxicity assay.

Human hematopoietic target-cell lines known to be lysable in short-term 51Cr-release assays by natural killer (NK) cells occurring in spleens of normal, nonimmune CBA/J and A/J mice were adapted to grow in culture medium supplemented with human AB serum or with normal mouse serum (NMS). After a culture period of more than 8 weeks, the resulting AB serum- or NMS-grown sublines exhibited the same degree of sensitivity to mouse NK cells in direct or competition assays as the original lines kept in fetal calf serum. Susceptibility of the various target cell lines was also independent of the type of serum supplement used during the cytotoxicity assay. Preabsorption of the serum supplement with in vitro cultured cell lines identical to the target cells left NK cytotoxicity to these lines intact. In this heterologous system, no changes in the expression of NK relevant target structure(s) could be detected in sublines grown in sera from different species, but target susceptibility seemed to be preserved.

ABO Blood-Group System↗
PubMed1978

Corynebacterium parvum-induced peritoneal exudate cells with rapid cytolytic activity against tumour cells are non-phagocytic cells with characteristics of natural killer cells.

Peritoneal exudate cells taken from mice 3 days after intraperitoneal treatment with Corynebacterium parvum (Cp) have been shown to kill specifically certain tumour targets in vitro. We have analysed in detail such Cp-induced cytotoxic cells as to their cellular characteristics, considering the fact that size and charge characteristics of cellular subgroups are useful markers in describing their representative characteristics. We could thus show that the cytolytic cell could not be classified as a macrophage. They behaved, in every manner analysed, exactly as the previously defined natural killer cells found in the lymphoid organs of normal mice.

Animals↗
PubMed1977

Generation of natural killer cells: an autonomous function of the bone marrow.

Generation of natural killer (NK) cells in spleens from radiation chimeras produced between pairs of histocompatible 'high' and 'low' NK-reactive mouse strains has been investigated. Spleen cells of high-reactive recipients reconstituted with bone marrow from low-reactive mice were found to be low reactive. Conversely, spleen cells of low mice grafted with bone marrow or fetal liver cells from high donors were high reactive. Similarly, the age-related changes of NK activity were shown to be expressed at the bone marrow precursor cell level. These results indicate that the generation of natural killer cells is an inborn and autonomous function of the bone marrow and does not depend on the genotype or other influences of the host environment.

Animals↗
PubMed1977

Suppression of natural killer cell activity with radioactive strontium: effector cells are marrow dependent.

NK cells with lytic capacity for Moloney leukemia virus-induced lymphomas have previously been found to occur spontaneously in spleens from nonimmune adult mice. Here, 89Sr-treatment is shown to suppress NK cell function in adult mice without similarly affecting other cell-mediated immune reactions. Thus, selective 89Sr-sensitivity distinguishes NK cells from other killer cell types. The present results indicate that in vivo a functional bone marrow is needed for generation and maintenance of NK activity.

Animals↗
PubMed1976

Genetically determined resistance to infection by hepatotropic influenza A virus in mice: effect of immunosuppression.

Mice carrying the gene Mx were resistant to the lethal action of a hepatotropic line of avian influenza A virus. In resistant animals, foci of liver necrosis were self-limiting, and maximal virus titers reached were much below those in susceptible animals. Resistance could not be abrogated by immunosuppressive treatment with cyclophosphamide, methotrexate, or procarbazine, although such treatment prevented cellular infiltration at sites of virus replication and appeared to delay virus clearance. Silica and thorium dioxide, thought to inhibit macrophage function, likewise failed to abolish resistance. Regenerating liver tissue did not support more extensive virus replication than did intact adult liver.

Animals↗
PubMed1976

Pathology of influenza hepatitis in susceptible and genetically resistant mice.

Mice resistant (homozygous or heterozygous for the gene Mx) and mice susceptible to the lethal effect of influenza viruses were inoculated intraperitoneally and intraportally with a hepatotropic variant of influenza A virus. Disease evolution was followed histologically and by immunofluorescence. In susceptible animals, rapidly spreading foci of hepatocyte necrosis with little inflammatory infiltration was observed. Death occurred on the 3rd day, when the entire liver was involved. In resistant animals foci became detectable later, and were fewer and smaller. They were infiltrated by cells morphologically resembling liver macrophages (Kupffer cells), and they regressed from the 4th day after infection. Barriers to virus spread appeared to be present at all stages of the disease.

Animals↗