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Query: UMLS:C0026918 (Mycobacterium)
 52,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two series of experiments were carried out using 66 guinea pigs infected with tuberculosis. In the first experiment generalized tuberculosis was stimulated by means of subcutaneous administration of Mycobacterium tuberculosis H37RV strain at a dose of 0.0001 mg. In the second experiment destructive form of tuberculosis was developed after intrapulmonary administration of the bacteria (1 mg) followed by VCG vaccination. In both experiments the animals were divided into groups with spontaneous form of the infection and the group of animals treated with rifamycin and isoniazid. Total protein, elastolytic activity, cathepsins B and D, free antitryptic activity were estimated in lung homogenates. Generalized and destructive forms of tuberculosis were shown to induce an increase in content of soluble protein as well as in cathepsin D, elastolytic and antitryptic activities in tissues. Destructive form of tuberculosis was characterized by more than 4-fold increase in elastolytic activity and by a distinct activation of cathepsin B. The antibacterial drugs used affected only slightly the biochemical patterns studied in lung tissue.
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PMID:[Comparative characteristics of the activity of proteolytic enzymes and their inhibitors in the lung tissue of guinea pigs during development of generalized and destructive tuberculosis]. 353 49

We have used the cryosection immunogold technique to study the composition of the Mycobacterium tuberculosis phagosome. We have used quantitative immunogold staining to determine the distribution of several known markers of the endosomal-lysosomal pathway in human monocytes after ingestion of either M. tuberculosis, Legionella pneumophila, or polystyrene beads. Compared with the other phagocytic particles studied, the M. tuberculosis phagosome exhibits delayed clearance of major histocompatibility complex (MHC) class I molecules, relatively intense staining for MHC class II molecules and the endosomal marker transferrin receptor, and relatively weak staining for the lysosomal membrane glycoproteins, CD63, LAMP-1, and LAMP-2 and the lysosomal acid protease, cathepsin D. In contrast to M. tuberculosis, the L. pneumophila phagosome rapidly clears MHC class I molecules and excludes all endosomal-lysosomal markers studied. In contrast to both live M. tuberculosis and L. pneumophila phagosomes, phagosomes containing either polystyrene beads or heat-killed M. tuberculosis stain intensely for lysosomal membrane glycoproteins and cathepsin D. These findings suggest that (a) M. tuberculosis retards the maturation of its phagosome along the endosomal-lysosomal pathway and resides in a compartment with endosomal, as opposed to lysosomal, characteristics; and (b) the intraphagosomal pathway, i.e., the pathway followed by several intracellular parasites that inhibit phagosome-lysosome fusion, is heterogeneous.
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PMID:Characterization of the Mycobacterium tuberculosis phagosome and evidence that phagosomal maturation is inhibited. 780 6

The success of Mycobacterium as a pathogen hinges on its ability to modulate its intracellular environment. Mycobacterium avium reside in vacuoles with limited proteolytic activity, maintain cathepsin D in an immature form and remain accessible to internalized transferrin. Artificial acidification of isolated phagosomes facilitated processing of cathepsin D, demonstrating that pH alone limits proteolysis in these vacuoles. Moreover, analysis of IgG-bead phagosomes at early time points during their formation indicates that these phagosomes also acquire LAMP 1 and cathepsin D prior to the accumulation of proton-ATPases, and are transiently accessible to sorting endosomes. This suggests that the anomolous distribution of endosomal proteins in M. avium-containing vacuoles results from their arrested differentiation in an early transitional stage through which all phagosomes pass.
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PMID:Mycobacterium-containing phagosomes are accessible to early endosomes and reflect a transitional state in normal phagosome biogenesis. 900 72

We characterized the Mycobacterium marinum phagosome by using a variety of endocytic markers to follow the path of the bacteria through a mouse macrophage cell line. Using a laser confocal microscope, we found that the majority of viable M. marinum cells were in nonacidic vacuoles that did not colocalize with the vacuolar proton ATPase (V-ATPase), the calcium-independent mannose-6-phosphate receptor (CI-M6PR), or cathepsin D. In contrast, heat-killed organisms and latex beads were in acidic vacuoles which contained the V-ATPase, the CI-M6PR, and cathepsin D. A population of vesicles that contained live M. marinum labeled with the lysosomal glycoprotein LAMP-1, but the percentage of vacuoles that labeled was lower than for heat-killed organisms or latex beads. When testing live and heat-killed Mycobacterium tuberculosis, we found levels of colocalization with LAMP- and cathepsin D comparable to those for the M. marinum isolate. We conclude that M. marinum, like M. tuberculosis, can circumvent the host endocytic pathway and reside in an intracellular compartment which is not acidic and does not fuse with lysosomes. In addition, we describe a system for sampling a large population of intracellular organisms by using a laser confocal microscope.
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PMID:Differential trafficking of live and dead Mycobacterium marinum organisms in macrophages. 911 92

We have evaluated the uptake of a soluble protein antigen, denitrophenylated human serum albumin (DNP-HSA), and two different intracellular bacteria; Chlamydia trachomatis serovar L2 and Mycobacterium tuberculosis strain H37Ra, by immature human dendritic cells. These were generated by culturing progenitor cells from blood in the presence of cytokines (granulocyte-macrophage colony-stimulating factor and interleukin-4). Dendritic cells play a crucial part in antigen presentation for the induction of T-cell-dependent immune responses in various tissues. Recently, macropinocytic and phagocytic activity has been shown for immature dendritic cells of mouse, rat and human origin. In the present study, macropinocytosis characterized the uptake of the soluble protein-antigen DNP-HSA, whereas the C. trachomatis were ingested via receptor-mediated endocytosis in coated pits, and opsonized M. tuberculosis via phagocytosis. To follow the intracellular routes of the antigens, their positions were compared with the localization of annexins, a family of Ca(2+)-and phospholipid-binding proteins, involved in membrane fusion, aggregation and transport of different vesicles. To elucidate further the intracellular pathway of the antigens, two other proteins, lysosome-associated membrane protein-1 (LAMP-1) and cathepsin D, were labelled. They are known to colocalize with major histocompatibility complex class II compartments in the immature dendritic cells. We observed a distinct translocation of annexin V to DNP-HSA containing endosomes, and annexin III to vesicles with C. trachomatis. Furthermore, annexin III, IV and V redistributed to phagosomes with M. tuberculosis. Both LAMP-1 and cathepsin D colocalized with DNP-HSA endosomes, and with phagosomes with M. tuberculosis. Thus, immature human dendritic cells have the capacity to phagocytose. Moreover, the handling of these antigens by dendritic cells may represent three distinct intracellular pathways, albeit some properties and compartments are shared.
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PMID:Role of annexins in endocytosis of antigens in immature human dendritic cells. 949 92

Phagosome maturation is characterized by the sequential acquisition and loss of proteins by the phagocytic vacuole during the formation of an acidic and hydrolytic compartment where degradation of the phagocytosed particle occurs. Transfer of proteins to the maturing phagosome occurs by fusion with a range of vesicles. Here we describe direct fusion of early phagosomes with vesicles that appear to be derived from the biosynthetic pathway. In mouse bone marrow macrophages, the 51 kDa proform of cathepsin D was found in vesicles of the ER/Golgi network that could be discriminated from endosomal vesicles which in turn contained the 46 and 30 kDa processed forms of the enzyme. Procathepsin D was acquired by phagosomes formed around inert particles such as IgG-coated beads and could be "protected" by blocking acidification with Bafilomycin A1. Mycobacterium avium-containing vacuoles from established infections possessed both pro- and processed cathepsin D similar to early bead-containing phagosomes. In contrast phagosomes harboring dead mycobacteria demonstrated markedly enhanced acquisition of the 46kDa form within 4 h post internalization and only low levels of procathepsin D.
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PMID:Direct delivery of procathepsin D to phagosomes: implications for phagosome biogenesis and parasitism by Mycobacterium. 1056 46

By applying density gradient electrophoresis (DGE) to human macrophages infected with Mycobacterium bovis BCG, we were able to separate three different bacterial fractions representing arrested phagosomes, phagolysosomes and mycobacterial clumps. After further purification of the phagosomal population, we found that isolated phagosomes containing live BCG were arrested in maturation as they exhibited only low amounts of the lysosomal glycoprotein LAMP-1 and processing of the lysosomal hydrolase cathepsin D was blocked. In addition, low amounts of MHC class I and class II molecules and the absence of HLA-DM suggest sequestration of mycobacterial phagosomes from antigen-processing pathways. We further investigated the involvement of the actin-binding protein coronin in intracellular survival of mycobacteria and showed that human coronin, as well as F-actin, were associated with early stages of mycobacterial phagocytosis but not with phagosome maintenance. Therefore, we conclude that the unique DGE migration pattern of arrested phagosomes is not as a result of retention of coronin, but that there are other proteins or lipids responsible for the block in maturation in human macrophages.
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PMID:Coronin is involved in uptake of Mycobacterium bovis BCG in human macrophages but not in phagosome maintenance. 1173 91

To clarify what kinds of proteinases are secreted into the foci of allergic-inflammation involving delayed-type hypersensitivity reaction, we examined the characteristic releases of various proteinases into the foci of Mycobacterium tuberculosis (M. tuber.)-induced delayed-type allergic-inflammation in mice. The significant activities of cathepsin B and prolylendopeptidase were observed in the washing-fluids of subcutaneous inflammatory foci of M. tuber.-induced delayed-type allergic-inflammation, but not M. tuber.-induced acute-inflammation. The SDS-resistant complex of cathepsin B and a protein substrate with apparent molecular mass of 74 kDa was observed by Western blot analysis. On the other hand, no significant accumulations of other proteinases, such as matrix metalloproteinases, cathepsin D, and serine proteinases, were determined. CA-074, a specific inhibitor of cathepsin B, suppressed both swelling and cathepsin B activity in the footpad having M. tuber.-induced delayed-type allergic-inflammation in vivo. These results suggest that cathepsin B may play an important role in the formation of M. tuber.-induced delayed-type allergic-inflammation.
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PMID:Significant accumulations of cathepsin B and prolylendopeptidase in inflammatory focus of delayed-type hypersensitivity induced by Mycobacterium tuberculosis in mice. 1500 14

Studies were undertaken to find out the effects of low frequency pulsed electromagnetic field (PEMF) in adjuvant induced arthritis (AIA) in rats, a widely used model for screening potential therapies for rheumatoid arthritis (RA). AIA was induced by an intradermal injection of a suspension of heat killed Mycobacterium tuberculosis (500 mug/0.1 ml) into the right hind paw of male Wistar rats. This resulted in swelling, loss of body weight, increase in paw volume as well as the activity of lysosomal enzymes viz., acid phosphatase, cathepsin D, and beta-glucuronidase and significant radiological and histological changes. PEMF therapy for arthritis involved optimization of three significant factors, viz., frequency, intensity, and duration; and the waveform used is sinusoidal. The use of factorial design in lieu of conventional method resulted in the development of an ideal combination of these factors. PEMF was applied using a Fransleau-Braunbeck coil system. A magnetic field of 5 Hz x 4 muT x 90 min was found to be optimal in lowering the paw edema volume and decreasing the activity of lysosomal enzymes. Soft tissue swelling was shown to be reduced as evidenced by radiology. Histological studies confirmed reduction in inflammatory cells infiltration, hyperplasia, and hypertrophy of cells lining synovial membrane. PEMF was also shown to have a membrane stabilizing action by significantly inhibiting the rate of release of beta-glucuronidase from lysosomal rich and sub-cellular fractions. The results indicated that PEMF could be developed as a potential therapy in the treatment of arthritis in humans.
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PMID:Optimization of pulsed electromagnetic field therapy for management of arthritis in rats. 1588 57

Lysophosphatidic acid (LPA) is a polar lipid metabolite which is involved in a wide range of biological processes, including cell proliferation and migration, wound healing, and increase of endothelial permeability. The present study reports evidences showing that LPA is able to enhance the antimicrobial activity of human macrophages and of bronchoalveolar lavage cells from tuberculosis patients leading to intracellular growth control of Mycobacterium tuberculosis. Such antimicrobial activity is mediated by the activation of phospholipase D which in turn induces acidification of M. tuberculosis containing phagosomes and is associated with the enhanced expression of Cathepsin D. These results suggest the possible protective role of this lysophospholipid in the activation of innate antimycobacterial response.
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PMID:Lysophosphatidic acid enhances antimycobacterial activity both in vitro and ex vivo. 1687 78


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