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

The cellular uptake by human neutrophils and the intraphagocytic biological activity of the new macrolide antimicrobial agent dirithromycin (0.01-2 mg/L) compared with erythromycin was investigated in vitro. Staphylococcus aureus, Listeria monocytogenes and Legionella pneumophila were used as the test intracellular microbial pathogens. After coincubation (45 min at 37 degrees C) of neutrophils with a fixed concentration of 2 mg/L of each antibiotic the respective intracellular/extracellular ratios for erythromycin and dirithromycin were 6.1 +/- 2.5 and 10.6 +/- 2 respectively (P < 0.005). Using a combination of techniques (colony counting, radiometry and fluorescence microscopy) both erythromycin and dirithromycin at concentrations of 0.01 and 0.5 mg/L and higher, respectively, were found to possess dose-related intraphagocytic bacteristatic activity for each of the test microbial pathogens. The effects of dirithromycin and erythromycin (1-20 mg/L) on neutrophil chemotaxis and generation of reactive oxidants by these cells were also investigated in vitro. Both antimicrobial agents caused a dose-related stimulation of neutrophil migration which was associated with inhibition of leucoattractant-activated generation of superoxide and activity of the myeloperoxidase/H2O2/halide system. However, superoxide generation by neutrophils activited with opsonized zymosan or phorbol myristate acetate was unaffected by the macrolides. These findings demonstrate that dirithromycin accumulates in human neutrophils, is biologically active intracellularly and modulates leucoattractant-activated superoxide generation and chemotaxis.
 ...
PMID:Investigation of the in-vitro uptake, intraphagocytic biological activity and effects on neutrophil superoxide generation of dirithromycin compared with erythromycin. 133 69

Four strains of Legionella pneumophila of different virulence as identified by ability to produce pneumonia and death in guinea-pigs infected by a fine-particle aerosol were examined for factors which may intracellularly influence virulence. Possible bactericidal mechanisms possessed by alveolar phagocytes were examined. A relationship could be established between resistance to H2O2, catalase activity and virulence amongst the strains. Virulent strains resisted the bactericidal activity generated by the xanthine oxidase system; avirulent strains did not. Incorporation of various specific inhibitors of the xanthine oxidase system indicated that the main bactericidal activities were associated with the production of H2O2 and hydroxyl radicals (.OH). All strains of L. pneumophila were susceptible to the bactericidal activity generated by the myeloperoxidase-H2O2-halide system, confirming earlier observations that polymorphonuclear neutrophil leucocytes (PMNLS) are able to kill both virulent and avirulent strains of L. pneumophila.
 ...
PMID:The effect of oxygen-dependent antimicrobial systems on strains of Legionella pneumophila of different virulence. 301 84

Legionella pneumophila was susceptible to the antimicrobial action of oxygen metabolites generated by both the myeloperoxidase-H(2)O(2)-halide and the xanthine oxidase systems.
 ...
PMID:Effect of oxygen-dependent antimicrobial systems on Legionella pneumophila. 629 60

Legionella pneumophila is a gram-negative microorganism that causes a severe pneumonia known as "legionnaires disease." Toll-like receptor 4 (TLR4) transduces the lipopolysaccharide signal and is therefore considered to play a role in host defense against gram-negative bacterial infection. To determine the role of TLR4 in L. pneumophila pneumonia, C3H/HeJ mice, which display a nonfunctional gene encoding TLR4 (TLR4), and wild-type (wt) C3H/HeN mice were intranasally inoculated with L. pneumophila serogroup 1. Infection proceeded in an identical way in TLR4 mutant and wt mice, as reflected by similar bacterial outgrowth in the lungs. In addition, the inflammatory responses to L. pneumophila infection-as assessed by histopathologic analysis, cell influx in bronchoalveolar lavage fluid, myeloperoxidase activity in lungs, and lung cytokine concentrations-were indistinguishable in TLR4 mutant and wt mice. These data suggest that, in this mouse model, TLR4 does not play a role in resistance to L. pneumophila.
 ...
PMID:Toll-like receptor 4 is not involved in host defense against pulmonary Legionella pneumophila infection in a mouse model. 1219 88

Intracellular, non capsulated atypical bacteria (Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionella pneumophila) colonise lower airways very often. Atypical bacteria cause acute infection and exacerbation of chronic inflammation of bronchial tree, mainly chronic obstructive pulmonary disease (COPD). They may trigger bronchial asthma and induce asthma exacerbation. These pathogens are often isolated in sputum of patients suffering from asthma and COPD in stable clinical stage, but opinion about eradication of bacteria in this situation is controversial. Lately, much attention has been paid to immunogenic possibilities of atypical bacteria, especially Chlamydia penumoniae in pathomechanisms of asthma and COPD. Macrolides from near a half century have been a therapeutic option against intracellular pathogens. These highly lipophylic compounds very easily penetrate cellular membrane, act on subunit 50S of ribosome decreasing reproduction of bacteria in infected epithelial cells. Universal anti-inflammatory action of macrolides is due to their influence on pro-inflammatory cells (neutrophils, eosinophils, lymphocytes CD8) and in consequence decrease of releasing inflammatory mediators (myeloperoxidase, elastase, leukotrien B4, interleukin 8).
 ...
PMID:[The role of intracellular bacteria in etiology of lower airways infection--therapeutic implications]. 1649 94