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dc.contributor.authorBal, Vineeta-
dc.date.accessioned2015-01-05T09:33:14Z-
dc.date.available2015-01-05T09:33:14Z-
dc.date.issued2011-04-
dc.identifier.urihttp://hdl.handle.net/123456789/450-
dc.description.abstractMacrophages and polymorphonuclear cells (PMNs) rapidly respond to microbial and immune inflammatory stimuli and die during these responses. We have shown earlier that many macrophage and PMN functions are compromised in x-linked immunodeficient (Xid) mice with functional deficiency in Bruton's tyrosine kinase (Btk). We now report that Btk-deficient macrophages show enhanced susceptibility to apoptotic death on exposure to the microbial and immune inflammatory signals bacterial lipopolysaccharide (LPS) and interferon-gamma (IFNγ) in vitro. In vivo in mixed bone marrow (BM) chimeras Btk deficiency leads primarily to loss of peripheral macrophage numbers without affecting BM development, suggesting a role of inflammation-induced apoptosis in regulating macrophage life span. Surprisingly, Btk deficiency does not affect macrophage apoptosis induced by DNA damage or CD95 engagement. Reactive nitrogen and oxygen species also do not contribute to inflammation-induced apoptosis, but apoptotic process involves loss of mitochondrial potential, shows increased activation of caspase 9 and enhanced loss of Bcl-xL. The lack of pro-survival signaling through the Btk-phosphotidylinositol 3-kinase-Akt pathway, and persistent MEK signaling, lead to enhanced death in Btk-deficient macrophages only downstream of inflammatory triggers. These data underline the complex role of Btk in the regulation of macrophage survival and function.en_US
dc.publisherSpringer Science+Business Media, LLCen_US
dc.titleRole of Bruton's tyrosine kinase in macrophage apoptosisen_US
dc.contributor.coauthorKhare, Anupriya-
dc.contributor.coauthorViswanathan, Bharathi-
dc.contributor.coauthorGund, Rupali-
dc.contributor.coauthorJain, Nidhi-
dc.contributor.coauthorRavindran, Balachandran-
dc.contributor.coauthorGeorge, Anna-
dc.contributor.coauthorRath, Satyajit-
dc.keywordInflammation, Lipopolysaccharide, Interferon-gamma, Mitochondriaen_US
dc.journalApoptosisen_US
dc.volumeno16en_US
dc.issueno4en_US
dc.pages334-346en_US
Appears in Collections:Immumo Biology- I, Publications

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