Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-2-3
pubmed:abstractText
Macrophages are critical effectors of bacterial clearance and must retain viability, despite exposure to toxic bacterial products, until key antimicrobial functions are performed. Subsequently, host-mediated macrophage apoptosis aids resolution of infection. The ability of macrophages to make this transition from resistance to susceptibility to apoptosis is important for effective host innate immune responses. We investigated the role of Mcl-1, an essential regulator of macrophage lifespan, in this switch from viability to apoptosis, using the model of pneumococcal-associated macrophage apoptosis. Upon exposure to pneumococci, macrophages initially upregulate Mcl-1 protein and maintain viability for up to 14 hours. Subsequently, macrophages reduce expression of full-length Mcl-1 and upregulate a 34-kDa isoform of Mcl-1 corresponding to a novel BH3-only splice variant, Mcl-1(Exon-1). Change in expression of Mcl-1 protein is associated with mitochondrial membrane permeabilization, which is characterized by loss of mitochondrial inner transmembrane potential and translocation of cytochrome c and apoptosis-inducing factor. Following pneumococcal infection, macrophages expressing full-length human Mcl-1 as a transgene exhibit a delay in apoptosis and in bacterial killing. Mcl-1 transgenic mice clear pneumococci from the lung less efficiently than nontransgenic mice. Dynamic changes in Mcl-1 expression determine macrophage viability as well as antibacterial host defense.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-10200550, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-10318868, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-10471580, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-10556161, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-10627603, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-10722631, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-10766760, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-10837489, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-10878765, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-10899909, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-11015441, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-11101871, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-11121062, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-11175253, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-11207583, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-11457886, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-11466611, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-11517432, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-11679919, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-11861619, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-12136132, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-12242151, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-12379681, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-12496428, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-12783855, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-12901848, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-12952922, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-14513426, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-14551881, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-14607941, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-14633975, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-15078892, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-15122313, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-15132983, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-2405761, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-7503812, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-7682708, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-7896880, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-7931080, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-7963517, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-8600156, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-8975927, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-9002967, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-9233632, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-9239394, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-9427612, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-9430630, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-9671497, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-9675101, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-9721092, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-9746790, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-9787159, http://linkedlifedata.com/resource/pubmed/commentcorrection/15650769-9989411
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9738
pubmed:author
pubmed:issnType
Print
pubmed:volume
115
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
359-68
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
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