More on Silver Spring monkeys.
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Animal Welfare↗
Biomedical subjects
S B Galsworthy
Publications and source records attributed to S B Galsworthy.
Chemotaxis in Listeria monocytogenes.
Listeria monocytogenes is a flagellated bacterium with a characteristic tumbling motion. It is intriguing to speculate that directional motility might facilitate penetration of the intestinal epithelium or selective colonization of the central nervous system or gravid uterus. There are conflicting reports on the extent of flagellation and degree of motility at temperatures corresponding to the internal environment of the mammalian host. No studies of chemotaxis in Listeria have been reported. We examined Listeria for flagella, motility, and chemotaxis after growth at 10 degrees, 24 degrees, 30 degrees, 37 degrees and 40 degrees C. Listeria grown at all temperatures possessed flagella and were motile to at least some degree. Those grown at 24 degrees or 30 degrees C were the most abundantly flagellated and the most vigorously motile. The bacteria were able to swim towards tryptose at all temperatures and toward glucose at all temperatures except 40 degrees C.
Cell Movement↗
Monocytosis producing activity from virulent and avirulent strains of Listeria.
Monocytosis is a hallmark of listeriosis in many species. A similar phenomenon is induced by a monocytosis-producing activity (MPA) purified from the organism. The relationship between MPA production and virulence is unclear. The purpose of this study was to measure MPA in extracts prepared from strains with known degrees of virulence and haemolysin production. Differential leukocyte counts on peripheral blood cells were performed 24, 48 and 72 h after injection of 0.5 mg MPA. In the strains we tested those known to be virulent produced monocytosis; those which were avirulent did not.
Animals↗
Genetic regulation of macrophage production in response to surface components of Listeria monocytogenes.
Resistance to murine listeriosis requires humoral factors which alter production or delivery of monocytes to infective foci. Production of such factors is under genetic control and may be modulated by bacterial components. Two components from Listeria monocytogenes, monocytosis producing activity (MPA) and immunosuppressive activity (ISA) were used to study monocytopoiesis in mice with known abnormalities in microphage-related functions. Listeria-sensitive A/J mice fail to produce or respond to MPA or an endogenous mediator of monocytosis (EF). These studies provided evidence that a second humoral factor, decreases monocytopoiesis. Sera from A/J mice are more active in this respect and MPA treatment increases the amount of inhibitory factor in A/J mice. A polyclonal B cell activator, ISA, which induces suppressor splenic macrophages, suppresses the anti-SRBC response in resistant B10. A mice but not in A/J mice. ISA induced no change in prostaglandin E2 production by spleen cells of either strain. One interpretation of these findings is that A/J mice after stimulation by ISA or MPA, produce a substance which inhibits development of mononuclear phagocytes.
Animals↗
Comparison of responsiveness to the monocytosis-producing activity of Listeria monocytogenes in mice genetically susceptible or resistant to listeriosis.
Injection of a monocytosis producing activity (MPA) from Listeria monocytogenes caused a dose-dependent elevation in numbers of macrophage colony forming units (CFU-m) in bone marrow and in peripheral blood. The increase could be seen as early as 8 h after injection of MPA and persisted until 72 h after injection. Serum from MPA-treated animals, capable of inducing monocytosis, also caused an elevation in numbers of CFU-m. The effect of MPA on CFU-m numbers in peripheral blood was measured in inbred strains of mice with differing susceptibility to listeriosis. Resistant C57B1/6 and B10. A mice responded best to MPA. C3H/HeJ and CBA mice, sensitive to Listeria, gave a slow, intermediate response. A/J mice, lacking the 5th component of complement, failed to respond to MPA. Since both B10.D2 old (C5-deficient) and B10.D2 new (C5-sufficient) mice, responded comparably to MPA, the unresponsiveness in A/J mice cannot be attributed solely to lack of C-5. Our results are consistent with the idea that A/J mice lack or are unresponsive to the MPA-induced serum factor which promotes monocytosis.
Animals↗
Effects of gold on the production of and response to human interleukin-1.
We studied the effects in vitro of sodium aurothiomalate (GSTM) on the production of, and response to, a monocyte supernatant with interleukin-1 (IL-1)-like activity. Monocyte supernatant was produced by human peripheral blood monocytes stimulated with lipoprotein polysaccharide, and its IL-1-like activity assayed by its effect on tritiated thymidine incorporation by C3H/HeJ mouse thymocytes. GSTM inhibited the thymocyte response to monocyte supernatant even when added to monocyte supernatant and thymocytes after 48 h of culture. GSTM also inhibited production of IL-1-like activity by monocytes, when added to culture within the first 22 h. Inhibition of both response to and production of monocyte supernatant was dose dependent. These effects of GSTM on Il-1-like activity may constitute one of the mechanisms of action of the drug in rheumatoid arthritis.
Adult↗
Concomitant induction of an inflammatory response and immunosuppression by an extract from Listeria monocytogenes.
An immunosuppressive agent (ISA) present in an aqueous extract from Listeria monocytogenes diminished the immune response in vivo to subsequently injected heterologous antigen. Intraperitoneal injection of ISA induced an inflammatory response and activation of the reticuloendothelial system, both of which coincided with the period of immune hyporesponsiveness. Mice treated with ISA exhibited increased accumulation of labelled antigen to phagocytic peritoneal cells but decreased delivery of labelled antigen to the spleen. Both delivery of antigen to spleen and the immune response could be improved by injecting either ISA or antigen or both intravenously, or by increasing the dose of antigen. The response of ISA-treated animals could also be improved by intraperitoneal injection of latex beads, colloidal carbon, or carrageenan shortly (60 min) before immunization. Spleen cells from ISA-treated mice adoptively transferred to irradiated syngeneic recipients were able to mount a normal immune response. These results suggest that ingestion of antigen by the enlarged population of phagocytes in peritoneal cavities of ISA-treated mice prevented antigen delivery to the spleen and was partly responsible for the observed immunosuppression.
Antibody Formation↗
Cytokinetics of mononuclear phagocyte response to listeriosis in genetically-determined sensitive and resistant murine hosts.
Genetically-determined differences in resistance to infection with L. monocytogenes are controlled by a single, non-H-2 linked gene Lr, which is expressed in some facet of the response of the mononuclear phagocyte system to listeriosis. In this study, the kinetics of monocyte production and turnover have been compared in Listeria-resistant B10.A and Listeria-sensitive A strain mice, in response to either listerial infection or stimulation with a water-soluble monocytosis-producing activity extracted from L. monocytogenes. Promonocyte generation time in resistant mice fell from approximately 17 to 13 h on the first day of infection, or several hours following injection of monocytosis-producing activity, whereas there was no such shortening of promonocyte generation time in susceptible mice at these times. Similarly, the half-time of circulating monocytes fell by approximately 8-9 h following listerial infection or injection of extracts of monocytosis-producing activity in resistant, but not in susceptible, mice. The Lr gene may, therefore, be controlling the production and emigration of mononuclear phagocytes shortly following infection, this in turn determining the degree of susceptibility of the host to listeriosis.
Animals↗
Immunomodulation by surface components of Listeria monocytogenes: a review.
Surface components of bacteria make the initial contact with host defence mechanisms. Such components from Listeria monocytogenes have been studied in attempts to elucidate mechanisms of pathogenicity. The cell walls of different serotypes of L. monocytogenes have been reported to contain abundant peptidoglycan, teichoic acid, lipoteichoic acid, endotoxin, and lipopeptidopolysaccharide. Cell walls are B cell mitogens in vivo and in vitro, fix complement, are chemotaxigenic and decrease resistance to infection with Listeria. A soluble, high molecular weight immunosuppressive agent is also a B cell mitogen in vitro. It induces an inflammatory response and a population of suppressor macrophages in vivo. Monocytosis-producing activity is a low molecular weight material associated with the cell membrane. It induces a labile, transient endogenous mediator and causes a 3-6 fold elevation in blood monocyte levels 48 h after injection. Mice genetically sensitive to Listeria infection fail to produce or respond to the endogenous monocytosis-inducing factor. The potential use of these factors in diagnosis of Listeria and in unravelling interrelationships in host defense mechanisms is discussed.
Adjuvants, Immunologic↗
Immunosuppression, nonspecific B-cell activation, and mitogenic activity associated with a high molecular weight component from Listeria monocytogenes.
A high molecular component of a saline extract derived from Listeria monocytogenes contained amino acids, carbohydrates, and phosphorus. The same fraction was capable of promoting both the in vitro mitogenic and adjuvant activities and the in vivo immunosuppressive activity displayed by the crude extract. The material was mitogenic to B but not to T lymphocytes in vitro. Responses to sheep and horse erythrocytes as well as to lipopolysaccharide were suppressed. Immunosuppression was dose dependent and was present at 1, 2, or 3 days but absent 7 days after injection. Both primary and secondary responses to sheep erythrocytes were impaired.
Adjuvants, Immunologic↗
Stimulation of monocyte production by an endogenous mediator induced by a component from Listeria monocytogenes.
A monocytosis-producing activity (MPA) is present in a saline-extractable material (SE) from Listeria monocytogenes. The mechanism of stimulation of monocyte production by SE was studied. Serum obtained from mice at appropriate times after injection of SE induced monocytosis in normal recipients. The monocytosis-inducing activity present in serum differed from SE with respect to timing of the monocytosis, fractionation pattern on a Sephadex G-200 column, and thermolability. The minimum dose of SE capable of producing a monocytosis was 100 micrograms. Antibody to SE capable of detecting SE at a concentration of greater than 5 micrograms/ml failed to detect SE in samples of active serum. Therefore it seemed highly unlikely that activity in serum was due to the presence of trace amounts of SE. The activity present in serum was thermolabile and had a molecular weight of about 38,000. The data are consistent with the hypothesis that injection of SE caused the production or release of an endogenous mediator capable of stimulating monocytosis.
Animals↗
Stimulation of monocyte precursors in vivo by an extract from Listeria monocytogenes.
A water-soluble monocytosis-producing activity (MPA) extracted from Listeria monocytogenes was found to stimulate proliferation of promonocytes in vivo. Mice were pulse-labelled for 2 h with tritiated thymidine ([3H]TdR) at various times after intraperitoneal injection of MPA. Autoradiography of bone marrow cells revealed an increased labelling index of promonocytes of MPA-treated mice which was maximum 8 h after the MPA injection. Mice labelled with [3H]TdR 8 h after MPA injection developed a monocytosis at the expected time (peak at 48 h) and the blood monocytes were found to be highly labelled. Both the generation time of monocyte precursors and the halftime of blood monocytes were found to be shorter than the corresponding values in control mice.
Animals↗
Immunological properties of partially purified material with monocytosis-producing activity from Listeria monocytogenes.
A fraction rich in a monocytosis-producing activity (MPA) has been obtained by a two-stage chromatographic separation from a saline extract (SE) of Listeria monocytogenes. Like SE, the purified material elicits monocytosis and decreases the halftime of circulating monocytes. The purification of MPA eliminates the following found in SE: the in vitro mitogenic activity, the in vitro adjuvant activity, the immunosuppressive activity, and the granulocytosis-promoting and the lymphopenia-inducing activities.
Animals↗
Purification of a monocytosis-producing activity from Listeria monocytogenes.
The monocytosis-producing activity (MPA) from Listeria monocytogenes is shown to be associated with the cell envelope. Both MPA and immunosuppressive activity were readily extracted with aqueous solvents and separated as two independent activities by gel filtration and ion-exchange chromatography. As little as 10 microng of the resulting MPA-containing fraction caused a ninefold elevation in the level of circulating monocytes. The molecular weight of the fraction was approximately 22,000, and it contained phosphorus and carbohydrate.
Carbohydrates↗
Sulfur-containing metabolites secreated by an ethionine-resistant mutant of Neurospora.
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Butyrates↗