Linked Life Data

16636015

Source:http://linkedlifedata.com/resource/pubmed/id/16636015

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2006-5-29
pubmed:abstractText
Mycobacterium tuberculosis-infected macrophages demonstrate diminished capacity to present antigens via class II MHC molecules. Since successful class II MHC-restricted antigen presentation relies on the actions of endocytic proteases, we asked whether the activities of cathepsins (Cat) B, S and L-three major lysosomal cysteine proteases-are modulated in macrophages infected with pathogenic Mycobacterium spp. Infection of murine bone marrow-derived macrophages with either Mycobacterium avium or M. tuberculosis had no obvious effect on Cat B or Cat S activity. In contrast, the activity of Cat L was altered in infected cells. Specifically, whereas the 24-kDa two-chain mature form of active Cat L predominated in uninfected cells, we observed an increase in the steady-state activity of the precursor single-chain (30 kDa) and 25-kDa two-chain forms of the enzyme in cells infected with either M. avium or M. tuberculosis. Pulse-chase analyses revealed that maturation of nascent, single-chain Cat L into the 25-kDa two-chain form was impaired in infected macrophages, and that maturation into the 24-kDa two-chain form did not occur. Consistent with these data, M. avium infection inhibited the IFNgamma-induced secretion of active two-chain Cat L by macrophages. Viable bacilli were not required to disrupt Cat L maturation, suggesting that a constitutively expressed mycobacterial component was responsible. The absence of the major active form of lysosomal Cat L in M. avium- and M. tuberculosis-infected macrophages may influence the types of T cell epitopes generated in these antigen-presenting cells, and/or the rate of class II MHC peptide loading.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0953-8178
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
931-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16636015-Animals, pubmed-meshheading:16636015-Antigen Presentation, pubmed-meshheading:16636015-Antigens, Bacterial, pubmed-meshheading:16636015-Bone Marrow Cells, pubmed-meshheading:16636015-Cathepsin B, pubmed-meshheading:16636015-Cathepsin L, pubmed-meshheading:16636015-Cathepsins, pubmed-meshheading:16636015-Cysteine Endopeptidases, pubmed-meshheading:16636015-Enzyme Activation, pubmed-meshheading:16636015-Epitopes, T-Lymphocyte, pubmed-meshheading:16636015-Genes, MHC Class II, pubmed-meshheading:16636015-Interferon-gamma, pubmed-meshheading:16636015-Macrophages, pubmed-meshheading:16636015-Mice, pubmed-meshheading:16636015-Mice, Knockout, pubmed-meshheading:16636015-Mycobacterium avium, pubmed-meshheading:16636015-Mycobacterium tuberculosis, pubmed-meshheading:16636015-Peptides, pubmed-meshheading:16636015-Protein Processing, Post-Translational, pubmed-meshheading:16636015-Tuberculosis
pubmed:year
2006
pubmed:articleTitle
Cathepsin L maturation and activity is impaired in macrophages harboring M. avium and M. tuberculosis.
pubmed:affiliation
Department of Microbiology, Ohio State University, 484 West 12th Avenue, Columbus, OH 43210, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't