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C Cheers

Publications and source records attributed to C Cheers.

At least 55 records · Page 3Linked to original sources
PubMed1990

Anti-bacterial activity of peritoneal cells from transgenic mice producing high levels of GM-CSF.

Two lines of transgenic mice carrying the gene for granulocyte-macrophage colony-stimulating factor (GM-CSF) produce vastly increased numbers of macrophages with abundant foamy cytoplasm resembling classical activated macrophages. Cells from both lines were negative for myeloperoxidase, a bactericidal enzyme found in monocytes as well as neutrophils, but not mature macrophages. Cells from the so called 'male line' produced greatly increased levels of oxygen degradation products in response to phagocytosis, compared with cells from the 'female line' or from normal littermates. The ability of the cells to phagocytose and lyse the intracellular bacterium Listeria monocytogenes was tested in vitro using radiolabelled organisms. Although the cells from transgenic mice were more highly phagocytic than cells from normal littermates, cells from either line were no more efficient than normal at lysing the bacteria they had phagocytosed. Nevertheless, because of the high phagocytic rate, more bacteria were exposed to lysis in the cells of transgenic mice, and the final outcome was a higher rate of bacteriolysis.

Animals↗
PubMed1990

In vivo IL-1 potentiates both specific and non-specific arms of immune response to infection.

Injection of 10(5) U interleukin-1 (IL-1) 4 hr before intravenous infection with Listeria monocytogenes hastens recovery of mice. This is accompanied not only by early stimulation of colony-forming cells in the spleen to levels higher than those in untreated, infected mice but also by accelerated activation of lymphokine-producing, specific T lymphocytes.

Adjuvants, Immunologic↗
PubMed1989

Stimulation of macrophage phagocytic but not bactericidal activity by colony-stimulating factor 1.

The ability of mouse peritoneal cells to phagocytose and lyse Listeria monocytogenes was measured after the cells were incubated with purified murine macrophage-specific colony-stimulating factor (CSF-1). Activation of combined phagocytic and bacteriolytic ability required 24 h, with an optimal dose of 1,000 U of CSF-1 per ml. No activation was achieved with a shorter period of incubation, known to be sufficient for GM-CSF to stimulate phagocytosis by granulocytes, and there was no advantage in longer exposure. After 24 h in 1,000 U of CSF-1, macrophages showed visibly increased spreading on the plastic petri dish. Activated cells examined microscopically showed an increase in the number of phagocytic cells and in the numbers of bacteria per phagocytic cell. This increased phagocytic ability was evident also in the increase in the amount of radioactivity associated with the cells following a 30-min incubation with radiolabeled bacteria. When these cells were carefully washed, the percentage of this initial uptake released during the next 2 h was not increased by pretreatment of the cells with CSF-1, showing that the effect of this growth factor was on phagocytosis of the bacteria not on the killing mechanisms per se.

Animals↗
PubMed1988

Production of colony-stimulating factors (CSFs) during infection: separate determinations of macrophage-, granulocyte-, granulocyte-macrophage-, and multi-CSFs.

After infection of mice with Listeria monocytogenes, elevated levels of colony-stimulating factors (CSFs) in the serum were quantitated by six different assays: ability to stimulate colony formation, the proliferation of 2 suspension of bone marrow cells (both measuring total colony-stimulating activity), a radioimmunoassay for macrophage-CSF (CSF-1), the WEHI-3B differentiation assay for granulocyte-CSF, and proliferation of 32D-c1-3 and FDC-P1 cell lines (specific for multi-CSF and either multi- or granulocyte-macrophage-CSFs, respectively). The great bulk of serum colony-stimulating activity represented macrophage- and granulocyte-CSFs, with small but measurable amounts of granulocyte-macrophage-CSF. The degree of elevation of serum CSF depended on the infecting dose used and the numbers of bacteria growing in the spleens and livers of the two mouse strains compared, i.e., L. monocytogenes-resistant C57BL/10 and susceptible BALB/cJ. The increase in serum CSFs occurred before the peak in bone marrow granulocyte-macrophage progenitors and before the reduction in bacterial numbers which follows the onset of specific cell-mediated immunity.

Animals↗
PubMed1988

Macrophage production during murine listeriosis: colony-stimulating factor 1 (CSF-1) and CSF-1-binding cells in genetically resistant and susceptible mice.

The concentration of the macrophage-specific colony-stimulating factor (CSF-1) and the numbers of bone marrow and spleen cells with specific receptors for that factor have been investigated in a number of mouse strains under normal conditions and after infection with the facultative intracellular bacterium Listeria monocytogenes. The CSF-1 concentration in serum and tissue was markedly elevated in infected mice, the degree of stimulation reflecting the dose of L. monocytogenes. The CSF-1 titer did not correlate with genetic resistance or susceptibility of the mice to L. monocytogenes. In contrast to the effect of lipopolysaccharide, Listeria infection was able to increase the level of CSF-1 in the lipopolysaccharide nonresponder strain C3H/HeJ. In line with earlier findings on colony-forming cells, cells bearing receptors for CSF-1 in uninfected susceptible BALB/cJ mice were only half those in resistant C57BL/6J mice. After infection the majority of these cells disappeared from the bone marrow and spleen cells of both resistant and susceptible mice. The number of CSF-1 receptor-bearing cells in the normal bone marrow may determine the degree of resistance to L. monocytogenes.

Animals↗
PubMed1987

Serum colony stimulating activity and colony forming cells in murine brucellosis: relationship to immunopathology.

Intravenous injection of mice with Brucella abortus vaccine strain 19, results in a chronic infection, immunity to which is dependent on T cell activation of the macrophages. A major feature of the infection is splenomegaly characterized by massive numbers of macrophages. We report here investigations of the haemopoietic precursors of macrophages, the colony forming cells (CFC), and the growth factors, colony stimulating factors (CSF), controlling their production. Comparison was made amongst three mouse strains, CBA, BALB/c and C57B1/10, as well as the F1 (CBA x BALB/c), which differ in the degree of splenomegaly developed and their ability to rid themselves of infection. The proportion of colony forming cells in the spleen peaked 2 to 3 weeks after infection and was higher in those strains which developed stronger splenomegaly. On the other hand there was no relation between colony forming cells and ability to control infection. Serum CSF also peaked 2-3 weeks post infection, with similar titres in all mouse strains studied. Bone marrow exhibited an early loss of total cellularity after infection followed by recovery. There was a sharp peak in the proportion of colony forming cells in the bone marrow 2 weeks post infection. Spleen and bone marrow CFC and serum CSF all returned to normal levels before infection was resolved.

Animals↗
PubMed1987

Particulate antigens may be reprocessed after initial phagocytosis for presentation to T cells in vivo.

Macrophages were pulsed with Listeria monocytogenes antigens by intraperitoneal injection prior to harvesting and thoroughly washing the cells. The pulsed macrophages were injected into the feet of Listeria-immune or naive mice to elicit a delayed hypersensitivity reaction. Where soluble Listeria antigen was used, presentation by donor macrophages to host T cells required identity within the I region of the H-2 complex. However, presentation of alcohol-killed Listeria organisms or of a living, temperature-sensitive mutant of Listeria was apparently not H-2 restricted. When T cells enriched in vitro for Listeria reactivity were injected into the feet of naive mice, they reacted in an H-2 restricted manner to antigen presented to them either by the pulsed macrophages or host cells apparently acquiring antigen from the original pulsed macrophages.

Animals↗
PubMed1986

The in vitro bactericidal activity of peritoneal and spleen cells from Listeria-resistant and -susceptible mouse strains.

Two days after Listeria-resistant (LrR) C57BL/10 mice were infected intraperitoneally with Listeria, their peritoneal macrophages demonstrated enhanced bactericidal activity beyond that seen in susceptible (LrS) BALB/c or CBA mice. Intravenous infection had no effect on peritoneal cell activity. The induction, but not expression, of the enhanced activity was radiosensitive. There was no significant difference between the strains with respect to the number of cells or cellular composition of the exudates. No difference in the in vitro chemotactic response of cells from the two strains could be demonstrated. Therefore there seems to be recruitment to the infected peritoneal cavity of C57BL/10 mice of young, efficiently bactericidal monocytes/macrophages. On the other hand, spleen cell bactericidal activity was intrinsically superior in C57BL/10 mice compared with BALB/c mice, possibly because, as a haemopoietic organ, the C57BL/10 spleen already contains high numbers of these efficient monocytes.

Animals↗
PubMed1986

Colony-forming cells and colony-stimulating activity during listeriosis in genetically resistant or susceptible mice.

Serum colony-forming activity (CSA) and colony-forming cells (CFC) of resistant (C57BL/10 ScSn) and susceptible (BALB/cJ) mice were studied during Listeria monocytogenes infection. Key findings were also checked in susceptible CBA/H mice. Prompt, bacterial dose-dependent increases in serum CSA were observed in all mice following infection. In response to the same challenge dose, serum CSA increased more in susceptible mice, possibly because rapid bacterial proliferation lead to high bacterial numbers. Thus CSA is not a limiting factor which accounts for the differences in Listeria resistance, but is produced in response to bacterial load. In uninfected mice, there were higher numbers of colony-forming cells in the bone marrow and spleen of resistant mice than in susceptible mice. By 24 hr postinfection there was a sharp drop in total cell numbers including CFC, in the bone marrow of resistant C57BL/10 ScSn mice. This coincides with the time when monocytes have been first observed in the blood of infected mice and when differences in bacterial growth between the mouse strains were first observable. Since the superior resistance of C57BL/10 mice has been shown to be radiosensitive, it is probable that this larger, readily mobilized reserve of monocyte/granulocyte precursors in the resistant mice plays an important role in early control of infection. The significance of this is discussed.

Animals↗
PubMed1985

Activation of non-specific cytotoxic cells in Listeria-susceptible and -resistant mouse strains.

An increase in macrophage tumouricidal activity in the spleen was demonstrated following intravenous infection of genetically resistant C57BL/10 mice with Listeria monocytogenes, but not after infection of BALB/c mice. However, tumouricidal macrophages appeared in the peritoneal cavity of both strains after infection, while NK cell activity was generally higher in BALB/c mice. The activation of tumouricidal macrophages and NK cells in the C57BL/B10 mice was T independent and, at least in the peritoneal cavity, radioresistant (600 rads). The relevance of these results to the genetic control of resistance to Listeria is discussed.

Animals↗
PubMed1984

Effect of splenectomy on production of interferon and colony-stimulating factor in Listeria monocytogenes-infected mice.

Splenectomy of mice genetically susceptible to Listeria monocytogenes genetically susceptible mouse strains increased their resistance to L. monocytogenes infection but had no effect on the course of infection in L. monocytogenes-resistant mice. However, splenectomy led to a dramatic decrease in the production of colony-stimulating factor and interferon after L. monocytogenes infection in all mouse strains examined.

Animals↗
PubMed1984

Pathogenesis and cellular immunity in experimental murine brucellosis.

Infection of mice with Brucella abortus strain 19 provides a most useful and interesting model in which to study chronic infection with intracellular bacteria. Most strains of mice develop a chronic infection. However, certain strains are better able to handle their infection. Long term bone marrow chimeras showed this to be due to bone marrow derived cells, rather than host physiology, although whether it is due T or B lymphocytes, macrophages or polymorphs is yet to be determined. In vitro treatment of lymphocytes from infected donors showed that the subpopulations transferring protection to naive mice was Thy 1+ 2+ Ia-. i.e. the same T cell which induces cell mediated immunity to Listeria. In vivo injection of an optimal regime of anti Ly1 monoclonal antibody exacerbated infection and removed the population of cells transferring immunity. Sub-optimal amounts of anti-Ly-1 abrogated IgG Brucella agglutinating antibody without affecting bacterial numbers, thus confirming the T dependence of IgG antibody and suggesting that it is not important in recovery from infection. Marked splenomegaly occurred about 3 weeks after infection of the mice. It was transferred by T lymphocytes and involved marked influx of macrophages, increased haemopoiesis, fibrin deposition and fluid in the spleen. Although the macrophages were immunosuppressive in vitro they did not appear to account for chronicity of infection. In seeking to account for this chronicity we have compared a number of aspects of the immune response in chronically infected mice and in mice which were able to control their infection. Although we have ruled out a number of possibilities, we have not yet established the basis of chronicity.

Animals↗
PubMed1984

Listeriosis in beige mice and their heterozygous littermates.

The ability to resist the facultative intracellular bacterium Listeria monocytogenes was not impaired in the beige mutants of C57BL/6J mice which are known to be deficient in a number of immune functions. The intravenous LD50 of Listeria in beige (bg/bg) mice and their normal heterozygous (bg +) littermates was approximately 5 X 10(5). Growth of Listeria in the spleen and liver during primary and secondary infections was similar in the two groups of mice, and each was able to act efficiently in adoptive transfer of immunity. Histological examination showed a normal accumulation of polymorphonuclear and mononuclear cells at foci of infection in the liver, while in the spleen the previously described depletion of T cells 2-4 days after infection was observed in both groups. In-vitro 18-hr cytotoxicity of peritoneal cells for P815 targets, a function usually attributed to macrophages, was increased 2 days after infection in both bg/bg and bg/+ mice. In contrast, 4 hr cytotoxicity of spleen cells for YAC-1 targets, considered typical of natural killer (NK) cells, was depressed in uninfected bg/bg mice and only slightly raised during infection. This compared with a normal NK activity in uninfected bg/+ mice which was markedly increased during infection.

Animals↗
PubMed1983

Restriction in adoptive transfer of resistance to Listeria monocytogenes. II. Use of congenic and mutant mice show transfer to be H-2K restricted.

Adoptive transfer of cell-mediated immunity to the facultative intracellular bacterium Listeria monocytogenes is restricted by the H-2 complex of mice. Using C57BL/10 and C57BL/6 congenic strains of mice it was shown that compatibility of the H-2K locus, not the I region, was essential and sufficient for adoptive transfer and that H-2D compatibility was not relevant. Mutation at the H-2K locus prevented adoptive transfer, while mutation at the Ia-1 locus, as in the B6.C-H-2bm12 mutant of C57BL/6, did not affect adoptive transfer. The contrast between these findings and the previously accepted I region restriction of adoptive transfer of Listeria immunity is discussed.

Animals↗
PubMed1983

Restriction in adoptive transfer of resistance to Listeria monocytogenes. I. Influence of non-H-2 loci.

In vivo adoptive transfer of T-cell-mediated immunity to the facultative intracellular bacterium Listeria monocytogenes is restricted, not only by the H-2 haplotype of the mice, but also by incompatibilities at non-H-2 loci. Thus, transfer between H-2 identical strains of mice with different background genes was reproducibly and significantly less efficient than transfer between completely syngeneic mice, although the restriction was less marked than that across the H-2 barrier. Restriction also occurred when parental cells were injected into semisyngeneic F1 hybrids and when cells from F1 hybrids were injected into parental strains. Using congenic strains of mice differing only at defined minor histocompatibility antigens, it was found that, of those loci available for study, antigens arising from the H-4 and H-8 loci strongly restricted transfer, whereas those specified by H-1, H-3, and H-7 did not.

Animals↗
PubMed1983

Resistance and susceptibility of mice to bacterial infection. IV. Functional specificity in natural resistance to facultative intracellular bacteria.

The effect of opsonic antibody on resistance of susceptibility of three strains of mice, C57Bl/10, BALB/c, and CBA to the intracellular bacteria Listeria monocytogenes, Salmonella typhimurium, and Brucella abortus was tested. Bacteria were opsonized by serum treatment before their injection into mice, or the mice were preimmunized by injection with alcohol killed bacteria which induces antibody without macrophage activation. Antibody did not increase the rate of clearance of Listeria from the bloodstream, nor did it affect the subsequent growth of that organism in the spleen and liver. Blood clearance of S. typhimurium and of B. abortus was increased by preopsonization with specific antibody, indicating that opsonins were a limiting factor in resistance to these two bacteria. However, neither opsonization before infection nor immunization with alcohol killed vaccines had any effect on the strain distribution of resistance/susceptibility, which differs for each of the three intracellular pathogens. Thus, even in the presence of adequate opsonization the three strains of mice showed different patterns of resistance/susceptibility to Listeria, S. typhimurium, and B. abortus. This implies that each has a unique cellular mechanism of early nonspecific resistance.

Animals↗
PubMed1982

Resistance and susceptibility of mice to bacterial infection. IV. Genetic and cellular basis of resistance to chronic infection with Brucella abortus.

The number of Brucella abortus strain 19 organisms in the spleens of CBA/H mice peaked two weeks after intravenous injection of 5 X 10(6) organisms. With the onset of specific cell-mediated immunity, 90% of the bacteria were killed, but approximately 10(6) bacteria persisted up to seven weeks after infection. In contrast, in BALB/c, C57BL/10, and B10Br mice, bacterial numbers peaked at two weeks but decreased steadily with the onset of bactericidal activity. In all strains, clearance of bacteria from the liver was relatively efficient. The course of infection in (CBA/H X BALB/c) F1 mice was similar to that in CBA/H mice, indicating that the mechanism(s) leading to slower recovery from infection was dominant. The H-2 haplotype of the mice did not influence the rate of recovery from infection. The use of backcross mice showed that multiple genes were involved. In bone marrow-chimeric mice, resistance was determined by the genome of the bone marrow donor, not that of the host.

Animals↗