Linked Life Data

9490634

Source:http://linkedlifedata.com/resource/pubmed/id/9490634

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1998-8-6
pubmed:abstractText
One of the major mechanisms permitting intracellular pathogens to parasitize macrophages is their ability to alter maturation of the phagosome or affect its physical integrity. These processes are opposed by the host innate and adaptive immune defenses, and in many instances mononuclear phagocytes can be stimulated with appropriate cytokines to restrict the growth of the microorganisms within the phagosomal compartment. Very little is known about the effects that cytokines have on phagosome maturation. Here we have used green fluorescent protein (GFP)-labeled mycobacteria and a fixable acidotropic probe, LysoTracker Red DND-99, to monitor maturation of the mycobacterial phagosome. The macrophage compartments that stained with the LysoTracker probe were examined first. This dye was found to colocalize preferentially with the late endosomal and lysosomal markers rab7 and Lamp1, and with a fluid phase marker chased into the late endosomal compartments. In contrast, LysoTracker showed only a minor overlap with the early endosomal marker rab5. Pathogenic mycobacteria are believed to reside in nonacidified vacuoles sequestered away from late endosomal compartments as a part of their intracellular survival strategy. We examined the status of mycobacterial phagosomes in macrophages from IL-10 knockout mice, in quiescent cells, and in mononuclear phagocytes stimulated with the macrophage-activating cytokine IFN-(gamma). When macrophages were derived from the bone marrow of transgenic IL-10 mice lacking this major deactivating cytokine, colocalization of GFP-fluorescing mycobacteria with the LysoTracker staining appeared enhanced, suggestive of increased acidification of the mycobacterial phagosome relative to macrophages from normal mice. When bone marrow-derived macrophages from normal mice or a J774 murine macrophage cell line were stimulated with IFN-(gamma) and LPS, this resulted in increased colocalization of mycobacteria and LysoTracker, but no statistically significant enhancement was observed in IL-10 transgenic animals. These studies are consistent with the interpretation that proinflammatory and anti-inflammatory cytokines affect maturation of mycobacterial phagosomes. Although multiple mechanisms are likely to be at work, we propose the existence of a direct link between cytokine effects on the host cell and phagosome maturation in the macrophage.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:volume
111 ( Pt 7)
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
897-905
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:9490634-Animals, pubmed-meshheading:9490634-Bone Marrow Cells, pubmed-meshheading:9490634-Cell Compartmentation, pubmed-meshheading:9490634-Cell Line, pubmed-meshheading:9490634-Cytokines, pubmed-meshheading:9490634-Endosomes, pubmed-meshheading:9490634-Fluorescent Dyes, pubmed-meshheading:9490634-Green Fluorescent Proteins, pubmed-meshheading:9490634-Hydrogen-Ion Concentration, pubmed-meshheading:9490634-Interferon-gamma, pubmed-meshheading:9490634-Interleukin-10, pubmed-meshheading:9490634-Luminescent Proteins, pubmed-meshheading:9490634-Lysosomes, pubmed-meshheading:9490634-Macrophages, pubmed-meshheading:9490634-Mice, pubmed-meshheading:9490634-Mice, Inbred C57BL, pubmed-meshheading:9490634-Mice, Knockout, pubmed-meshheading:9490634-Mycobacterium bovis, pubmed-meshheading:9490634-Phagosomes
pubmed:year
1998
pubmed:articleTitle
Effects of cytokines on mycobacterial phagosome maturation.
pubmed:affiliation
Department of Microbiology, University of Michigan, Ann Arbor, MI 48109, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.