Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023241 (Legionella)
 6,990 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Legionella pneumophila is a facultative intracellular parasite of alveolar macrophages. In vitro studies have shown that lymphokine-activated mononuclear phagocytes inhibit intracellular replication of L. pneumophila. To determine if recovery from legionellosis is associated with activation of alveolar macrophages in vivo to resist L. pneumophila, we studied an animal model of Legionnaires' disease. Rats were exposed to aerosolized L. pneumophila and alveolar macrophages were harvested during the recovery phase of infection. We compared these alveolar exudate macrophages with normal resident alveolar macrophages for the capacity to support or inhibit the intracellular growth of L. pneumophila. We also measured Ia expression as a marker of immunologic activation, and studied binding of bacteria, superoxide release, and the expression of transferrin receptors as potential mechanisms of resistance to L. pneumophila. For perspective on the specificity of these responses, we also studied alveolar exudate cells elicited by inhalation of heat-killed L. pneumophila, live Listeria monocytogenes, and live Escherichia coli. We found that alveolar exudate macrophages elicited by live L. pneumophila, but not heat-killed L. pneumophila, resisted the intracellular growth of L. pneumophila. Exudate macrophages in resolving legionellosis exhibited increased Ia expression, diminished superoxide production, and downregulation of transferrin receptors. Binding of L. pneumophila to exudate macrophages was indistinguishable from that to resident macrophages in the presence of normal serum, and augmented in the presence of immune serum. Alveolar exudate macrophages elicited by E. coli also inhibited growth of L. pneumophila, and exhibited a modest increase in Ia expression without change in transferrin receptors. Exudate cells induced by L. monocytogenes exhibited up-regulation of Ia without diminution of superoxide release. Alveolar cells harvested after inhalation of heat-killed L. pneumophila did not differ from resident alveolar macrophages in the expression of surface markers. These findings suggest that alveolar macrophages are immunologically activated in vivo to serve as effector cells in resolving legionellosis, and that live bacteria are required to induce this expression of immunity. The mechanism of resistance to parasitism by L. pneumophila may entail restriction of the intracellular availability of iron, but does not involve diminished bacterial binding or an augmented respiratory burst.
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PMID:Alveolar macrophage activation in experimental legionellosis. 164 46

Similar to guinea pig macrophages and human monocytes, macrophages from the peritoneal cavity of thioglycolate pretreated A/J mice are permissive for growth of Legionella pneumophila. In contrast, macrophages from BDF1 mice are not permissive for L. pneumophila. Lymphocytes from A/J and BDF1 mice proliferated in response to Legionella Ag but guinea pig lymphocytes did not. Also, splenocyte cultures from A/J mice treated with either Con A or Legionella vaccine produced supernatants which induced A/J macrophages to restrict Legionella growth, but guinea pig splenocyte culture supernatants obtained after stimulation with L. pneumophila vaccine did not induce Legionella growth restriction activity by guinea pig macrophages. Murine rIFN-gamma but not rIFN-alpha markedly inhibited growth of Legionella in A/J mouse macrophages and monoclonal anti-IFN-gamma antibody neutralized the anti-Legionella activity of culture supernatants from A/J mouse splenocytes responding to Legionella Ag. From these data, IFN-gamma appears to be an important factor in anti-Legionella activity of Ag-activated mouse splenocyte culture supernatants. Cyclosporin A, when given to either A/J or BDF1 mice, reduced the proliferation responses of splenocytes to T cell mitogens and also decreased the IFN production of A/J spleen cells to Legionella Ag. In addition, drug treatment decreased the resistance of A/J mice to Legionella infection as shown by an increase in the number of viable bacteria in the liver. However, injection of drug treated mice with lymphokine-rich splenocyte culture supernatant reconstituted the resistance of these animals. These results suggest an important role for lymphocyte activation and lymphokine production in the resistance of A/J mice to Legionella infection. The greater resistance of BDF1 mice, however, may result from nonpermissive macrophages and responsive lymphocytes. In the case of guinea pigs, susceptibility to Legionella infections may result from both the permissive nature of the macrophages and the relatively unresponsive nature of the lymphocytes in these animals.
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PMID:Differing macrophage and lymphocyte roles in resistance to Legionella pneumophila infection. 172 75

Legionella pneumophila (Lp) grow in cultures in human, guinea pig, and mouse macrophages from A/J strain mice. Because exudate macrophages from this strain of mice have been reported deficient in responsiveness to lymphokines, we thought it of interest to document the extent of responsiveness to interferon-gamma in the context of growth restriction of Lp. Peritoneal exudate macrophages were obtained from A/J mice and cultured in either the presence or absence of recombinant interferon-gamma. These cultures were then infected with Lp and the extent of bacterial growth estimated 48 hr later by means of a colony-forming unit (CFU) assay and electron microscopy. Interferon-gamma treatment significantly restricted the number of CFUs in the culture at concentrations as low as 20 U/ml, but did not affect the uptake of bacteria by macrophages. Furthermore, treatment with interferon induced morphological changes consistent with activated macrophages. The involvement of oxygen-dependent mechanisms in phagocyte killing and growth restriction was examined by the use of inhibitors such as superoxide dismutase (SOD) and catalase. Neither one of these inhibitors of toxic oxygen metabolites affected the interferon-gamma-induced suppression of Lp growth. These results suggest that although thioglycolate-induced exudate macrophages from A/J mice support the growth of Lp, these cells readily respond to the activating influence of interferon-gamma. Furthermore, lymphokine treatment does not inhibit Lp uptake by macrophages and apparently restricts the growth of bacteria by mechanisms independent of the activity of toxic oxygen metabolites.
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PMID:Interferon-gamma induced resistance to Legionella pneumophila in susceptible A/J mouse macrophages. 189 14

Previous reports have suggested a role for natural killer (NK) cells in directly lysing host cells infected with bacteria and other intracellular microorganisms. Here, we determined the inability of a highly homogeneous population of lymphokine activated killer (LAK) cells to kill macrophages infected with the following intracellular parasites: Mycobacterium avium, Listeria monocytogenes, Legionella pneumophila, Toxoplasma gondii, and Trypanosoma cruzi. In parallel cytotoxicity assays, LAK cells lysed the tumor targets YAC-1 and P815 effectively. Furthermore, we were able to demonstrate that influenza-specific cytotoxic T lymphocytes (CTL), but not LAK cells, were efficient killers of influenza virus-infected macrophages.
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PMID:A homogeneous population of lymphokine-activated killer (LAK) cells is incapable of killing virus-, bacteria-, or parasite-infected macrophages. 210 76

To determine if murine lymphocytes activated by interleukin 2 (IL-2) were cytotoxic against syngeneic elicited peritoneal macrophages (M phi) infected with intracellular pathogens, splenocytes that had been cultured with IL-2 for 5 or 10 days were studied in vitro. These cells, [lymphokine-activated killer (LAK) cells] showed significantly greater cytotoxicity against M phi infected with Leishmania major or Legionella pneumophila than against uninfected M phi. Preferential cytotoxicity against infected M phi was best shown using effector-to-target-cell ratios of 1:1-20:1; when ratios greater than or equal to 40:1 were employed, uninfected M phi were also lysed. The extent to which M phi that had been incubated with L. major were lysed depended upon the proportion of M phi containing intracellular organisms. After infection with L. major, the duration of incubation did not appear to influence the degree of lysis by LAK cells.
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PMID:Lysis of murine macrophages infected with intracellular pathogens by interleukin 2-activated killer (LAK) cells in vitro. 325 66