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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
|
pubmed:dateCreated |
1996-7-18
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pubmed:abstractText |
Graft-versus-host disease (GVHD) is associated with impaired B-cell responses. We investigated the mechanism of impaired proliferation of B cells in response to the mitogen lipopolysaccharide (LPS) by analyzing the production of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO), both of which have independently been described as important effector mechanisms in the pathogenesis of acute GVHD. A threefold decrease of mature surface Ig-positive (slg+) B cells was observed in GVHD spleens isolated 2 weeks after transplant. However, proliferation of these cells in response to LPS was suppressed by more than 35-fold. Activated GVHD splenocytes secreted large amounts of TNF-alpha and NO in culture. Neutralization of TNF-alpha with anti-TNF-alpha antibody (Ab) both abrogated NO production and restored LPS-induced proliferation of B cells to levels found in non-GVHD control mice. The specific inhibition of NO synthesis with LG-monomethyl-arginine (NMMA) restored splenocyte responses but did not significantly reduce TNF-alpha levels, showing that TNF-alpha per se did not cause immunosuppression. These data show that, during GVHD, induction of the NO pathway is an important mechanism that mediates B-cell hyporesponsiveness to LPS and that this pathway is induced by TNF-alpha.
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pubmed:grant | |
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
AIM
|
pubmed:chemical | |
pubmed:status |
MEDLINE
|
pubmed:month |
Apr
|
pubmed:issn |
0006-4971
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
1
|
pubmed:volume |
87
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
2853-60
|
pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:8639904-Animals,
pubmed-meshheading:8639904-B-Lymphocytes,
pubmed-meshheading:8639904-Cell Division,
pubmed-meshheading:8639904-Cells, Cultured,
pubmed-meshheading:8639904-Graft vs Host Disease,
pubmed-meshheading:8639904-Lipopolysaccharides,
pubmed-meshheading:8639904-Mice,
pubmed-meshheading:8639904-Nitric Oxide,
pubmed-meshheading:8639904-Tumor Necrosis Factor-alpha
|
pubmed:year |
1996
|
pubmed:articleTitle |
Suppression of B-cell proliferation to lipopolysaccharide is mediated through induction of the nitric oxide pathway by tumor necrosis factor-alpha in mice with acute graft-versus-host disease.
|
pubmed:affiliation |
Division of Pediatric Oncology, Dana-Farber Cancer Institute and Children's Hospital, Boston, MA, USA.
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|