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Query: UMLS:C0023241 (Legionella)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Legionella pneumophila-induced production of both membrane-associated and secreted interleukin 1 (mIL-1 and sIL-1, respectively) was examined utilizing peritoneal macrophages from BALB/c mice. The Legionella preparations for these studies included viable bacteria and formalin-killed whole cell preparations. Both of the preparations induced mIL-1 and sIL-1 in a dose-dependent fashion. However, the viable bacteria required about 1 log lower concentrations than the formalin-killed bacteria to induce the same level of IL-1 activity measured in the thymocyte proliferation assay. Kinetic studies showed that mIL-1 and sIL-1 were detectable within 4 hr after addition of either of the L. pneumophila preparations to the peritoneal macrophage cultures, with peak levels achieved within 24 hr. These results indicate that L. pneumophila is a potent inducer of both mIL-1 and sIL-1 in normal mouse peritoneal macrophage cultures.
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PMID:Induction of interleukin 1 by Legionella pneumophila in murine peritoneal macrophage cultures. 278 29

L. pneumophila is a facultative intracellular opportunistic pathogen ubiquitously present in the environment. Much is now known concerning the ecological niche of this organism as well as many other characteristics of these bacteria, including physiology and biochemistry. However, much less is known about immune mechanisms responsible for host resistance vs susceptibility. Not only outer membrane protein rich fractions but also LPS-rich components are potent immunogens, both in experimental animals such as susceptible guinea pigs and more resistant rodent species like rats and mice. Immunity to these organisms can be readily observed by a variety of serologic techniques. Antibody titers increase rapidly after exposure of individuals to these bacteria either by infection or immunization. However, such antibody does not appear to play an important role in host resistance. Serum antibody plus complement is not lytic for the bacteria in vitro. Furthermore, antibody appears to promote the phagocytosis of the bacteria by monocytes and/or macrophages in culture but such phagocytosis does not result in killing of the bacteria, merely an enhanced uptake and subsequent replication of the organisms. Studies on cellular immunity have focused attention on the role of T lymphocytes, monocytes and macrophages. In addition, cutaneous hypersensitivity is readily induced by infection or immunization of experimental animals with Legionella or antigenic components. In vitro correlates of hypersensitivity is also readily evident after infection or immunization. Although lymphoid cells from guinea pigs only show evidence of responsiveness to Legionella antigens by the lymphocyte blastogenic reaction after animals have been sensitized, peripheral blood monocytes from man as well as splenocytes from mice show evidence of responsiveness to Legionella even before known infection or sensitization. However, higher blastogenic responses become evident after sensitization or infection. In addition, interleukins, such as interleukin 1 and 2, as well as interferon and tumor necrotizing factor, appear in response to Legionella antigens and seem to play a role in resistance mechanisms. Cellular replication of Legionella in monocytes from man as well as macrophages from susceptible animals seems related to susceptibility or resistance to these organisms. Further analyses of the nature and mechanism of humoral vs cellular immune responses to Legionella antigens will provide valuable information about immunity and resistance to these intracellular pathogens in susceptible individuals.
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PMID:Legionella pneumophila immunity and immunomodulation: nature and mechanisms. 305 72

Exposure to Legionella pneumophila antigens has been reported to result in both an adjuvant effect and pathophysiological changes such as fever, headache, myalgia and arthralgias. Immunoenhancement and inflammatory changes have been associated with the production of interleukin 1, and we, therefore, sought an involvement of interleukin production in the alteration of biological responsiveness following exposure to Legionella pneumophila antigens. Killed Legionella pneumophila cells, incubated with mouse splenocytes, induced the formation of a soluble substance which enhanced splenocyte antibody production to heterologous antigen. The immunoenhancing substance was also produced by mouse peritoneal macrophages and supernatants from these cultures were demonstrated to also contain thymocyte co-mitogenic activity. Following gel filtration, this co-mitogenic activity eluted in the 15,000 molecular weight range suggesting an involvement of interleukin 1. Experiments with Legionella pneumophila cells, and cell extracts containing endotoxin, and purified endotoxin suggested that the interleukin 1 activity was induced by both endotoxin and non-endotoxin antigens. The Legionella pneumophila antigens were also found to be potent inducers of interleukin 1 activity in human peripheral blood mononuclear cell cultures. These results suggest that Legionella pneumophila antigens are potent inducers of interleukin 1 in both mouse and human cells. The induction of this monokine may partially account for both the immunoenhancing property of this bacterial species and the associated pathophysiological changes following infection with this microorganism.
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PMID:Induction of interleukin 1 by Legionella pneumophila antigens in mouse macrophage and human mononuclear leukocyte cultures. 349 24

Lipopolysaccharide isolated from Legionella pneumophila was found to be a potent antigen and inducer of antibody with strong adjuvant activity for related and unrelated antigens such as sheep erythrocytes by in vivo and in vitro systems. The LPS was also a potent stimulator of blastogenic responses by spleen cells from normal mice as well as from mice immunized with inactivated whole cells of Legionella. It strongly stimulated production of interferon and interleukin 1. These results indicate that the LPS of Legionella may be an important immune regulator in the host response.
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PMID:Immunogenicity and adjuvanticity of lipopolysaccharide from Legionella pneumophila. 380 73

Recent advances in the field of molecular biology have revolutionized our understanding of the functioning of living organisms and facilitated the development of robust tools for both diagnosis and treatment of diseases. With particular reference to the field of critical care medicine, development of molecular biology techniques have aided in the following: (1) rapid and highly specific detection of pathogenic infectious agents (eg, Mycobacterium tuberculosis, Pneumocystis carinii, cytomegalovirus, Legionella); (2) development of assays for measurement of circulating cytokines such as tumor necrosis factor (TNF) and interleukin (IL)-1 that has helped our understanding of the pathogenesis of the sepsis syndrome; (3) administration of antibodies or soluble receptors to attempt to prevent untoward effects of cytokines such as TNF or IL-1; and (4) the administration of recombinant deoxyribonucleic acid (DNA) or proteins to patients in an attempt to alter the course of a disease such as antioxidant enzymes (superoxide dismutase). The rapidity of progress in this field has been staggering, which necessitates frequent updating of our knowledge for clinicians to put these molecular tools to their best use. This brief review attempts to explain the basic principles of commonly used techniques in molecular biology including recombinant DNA, polymerase chain reaction, DNA libraries, gene therapy, and protein biochemistry in a manner that is understandable to those without an in-depth knowledge of the field.
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PMID:Current techniques in cell and molecular biology. 749 50

Bacterial heat shock proteins (hsp) have been shown to be important immunogens stimulating both T cells and B cells. However, little is known concerning the direct interactions between hsp and macrophages. In this study, we demonstrated that treatment of macrophage cultures with purified bacterial hsp, including Legionella pneumophila hsp60, Escherichia coli GroEL, Mycobacterium tuberculosis hsp70, Mycobacterium leprae hsp65, and Mycobacterium bovis BCG hsp65, increased the steady-state levels of cytokine mRNA for interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor as well as supernatant IL-1 secretion. This effect was shown not to be due to contamination of the hsp preparations with bacterial lipopolysaccharide. However, not all hsp induced cytokines; M. tuberculosis hsp10 showed minimal activity in our study. These results suggest that bacterial hsp might modulate immunity by rapidly and directly increasing cytokine production in macrophages.
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PMID:Bacterial heat shock proteins directly induce cytokine mRNA and interleukin-1 secretion in macrophage cultures. 796 Jan 55

Peritoneal exudate macrophages from A/J mice activated by purified lipid A preparations from Pseudomonas vesicularis, which contain 2,3-diamino-2,3-dideoxy-D-glucose disaccharide phosphomonoester as the lipid A backbone, restricted the growth of Legionella pneumophila, an intracellular opportunistic bacteria which readily grows in otherwise permissive macrophages from susceptible A/J mice and induced production of the proinflammatory cytokines interleukin 1 and tumor necrosis factor alpha. Activation of the macrophages was similar to that which occurred after stimulation with more conventional lipid A from other bacteria such as salmonellae. A purified fraction A3 preparation from the Pseudomonas lipid A, which lacked only 1 mol of amide-linked fatty acid, in comparison with another fraction (A2), which contained the fatty acid, also markedly activated the usually permissive macrophages from susceptible A/J mice to resist growth of the legionellae. The fraction A3 also induced both interleukin and tumor necrosis factor alpha. These results show that this novel lipid A from P. vesicularis can activate macrophages to resist infection with an opportunistic bacterium in a manner similar to that induced by conventional enterobacterial lipid A and that the hydrophobic portion of this Pseudomonas molecule may have an important role in activation of macrophages.
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PMID:Legionella pneumophila growth restriction and cytokine production by murine macrophages activated by a novel Pseudomonas lipid A. 830 Feb 34

The ability of antibody specific for Legionella pneumophila to enhance the induction of interleukin 1 (IL-1) production by murine peritoneal, splenic, and pulmonary macrophages in response to the bacterium was examined. Two preparations of L. pneumophila were utilized, a formalin-killed whole-cell preparation and viable bacteria. We measured both secreted (sIL-1) and cell membrane-associated (mIL-1) activities after incubation of the macrophages with the bacterial preparations in the presence or absence of the antibody. Both bacterial preparations induced sIL-1 and mIL-1 activities in each of the macrophage populations tested. These activities were generally enhanced by pretreating the bacteria with antibody, with the greatest enhancing activity observed for the formalin-killed preparations at lower doses of bacteria.
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PMID:Antibody-mediated enhancement of Legionella pneumophila-induced interleukin 1 activity. 840 89

Heat-shock proteins (hsp) are chaperon molecules important in protein folding and assembly. Furthermore, they may have functions in immunoregulatory processes, like T-cell stimulation and antigen presentation, which are not yet fully understood. It has been shown that several hsp of various species and family derivations modulate functions in macrophage immunity by directly increasing cytokine production. In the present study we showed that the 60,000 MW hsp of Legionella pneumophila (Lp-hsp 60) increased cellular steady-state levels of interleukin-1 beta (IL-1 beta) mRNA measured by quantitative reverse transcription-polymerase chain reaction and Northern blotting as well as IL-1 secretion, when added to cultures of thioglycollate-elicited mouse peritoneal macrophages in vitro. The level of mRNA increased in a dose-dependent manner with a minimum effective concentration of 0.5 microgram/ml and peaked 3 hr after stimulation. Lp-hsp 60-coated latex beads also increased IL-1 beta mRNA levels in the presence of cytochalasin D, which inhibits bead uptake but permits binding, indicating that binding to the macrophage surface was sufficient for induction. Accumulation of IL-1 beta mRNA was completely blocked by pretreatment with the protein kinase C (PKC) inhibitor, H7, but not decreased by prior treatment with cycloheximide. The cell lysates of macrophages stimulated with Lp-hsp 60 showed an increased PKC activity measured by phosphorylation of PKC pseudosubstrate. The IL-1 bioactivity in culture supernatants after 24 hr of stimulation with Lp-hsp 60 was increased in a dose-dependent manner but at hsp concentrations in excess of those needed to increase mRNA. Thus, the present study demonstrates that Lp-hsp 60 rapidly increases the steady-state level of IL-1 beta mRNA, possibly through a cell surface receptor system involving a PKC-dependent signalling pathway.
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PMID:Legionella pneumophila heat-shock protein-induced increase of interleukin-1 beta mRNA involves protein kinase C signalling in macrophages. 894 27

Marijuana contains both psychoactive and nonpsychoactive cannabinoids which have varying effects on the immune response system. Previous studies with delta-9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, showed that this substance augmented the susceptibility of mice to infection with the opportunistic pathogen Legionella pneumophila. The present study compared the enhancement of Legionella-induced mortality in mice due to two other major of marijuana components, cannabinol and cannabidiol, as well as the synthetic psychoactive cannabinoid CP 55,940. Inbred BALB/c mice, relatively resistant to infection with Legionella, were given the marijuana component 1 day before and 1 day after a sublethal intravenous infection with Legionella. Unlike the effect of THC, an 8 mg/kg dose of either cannabinol or cannabidiol did not affect mortality of the mice sublethally infected with Legionella. Mice given a 16 mg/kg dose of these components of marijuana, however, showed a slight to moderately increased mortality following the sublethal infection with Legionella. In contrast, a dose of 6 mg/kg of the synthetic psychoactive cannabinoid CP 55,940 given 1 day before and 1 day after infection with Legionella resulted in about 50% of the animals dying, the same level of augmentation of lethality induced by THC. Liver, spleen, and lung tissues were removed from the surviving mice 24 hr after the second THC injection and tested for the presence of viable Legionella using a standard CFU assay. The mice injected with THC before and after infection showed significantly higher levels of bacteria in their lung than mice that were not given any cannabinoid but were infected sublethally with the Legionella. Mice injected with the other cannabinoids, including the synthetic cannabinoid, showed a much smaller increase in the number of Legionella in their lung when infected with Legionella and treated with the drug. The number of bacteria recovered from the kidney and liver of the mice regardless of treatment with a cannabinoid, including with THC, did not show significant changes. RNA isolated from the spleen of the THC- and Legionella-treated animals was examined to determine at the molecular level whether acute phase pro-inflammatory cytokines (i.e., IL-1, IL-6 and TNF-alpha) were altered following drug treatment and infection, since previous studies had shown there were increased serum levels of these cytokines in the mice. It was found that the mRNA levels for IL-1 remained generally constant regardless of whether the infected animals were treated with a cannabinoid. However, the mRNA level for IL-6 was markedly increased following treatment of the infected animals with THC, suggesting the possible involvement of this pro-inflammatory cytokine in increased mortality. The mRNA level for TNF-alpha was generally low and not significantly altered in the drug treated animals. Mice given other cannabinoids, including cannabinol and cannabidiol, as well as the synthetic CP 55,940, showed no significant change in the level of mRNA for any of the cytokines tested.
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PMID:Psychoactive cannabinoids increase mortality and alter acute phase cytokine responses in mice sublethally infected with Legionella pneumophila. 901 63


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