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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2003-9-23
pubmed:abstractText
Chronic graft-versus-host disease (cGVHD) is a severe and frequent complication of allogenic bone marrow transplantation which is often treated with extracorporeal photochemotherapy (ECP) with a positive clinical outcome in patients resistant to conventional protocols. The mechanism of action of ECP has not been fully elucidated, although several authors have reported that it is able to induce apoptosis. Using samples obtained from ten cGVHD patients, we sought to determine whether lymphocytes treated with ECP underwent apoptosis and, above all, the mechanisms involved. Lymphocytes at four stages were isolated: immediately before ECP, from the last buffy coat collected, after UV irradiation prior to reinfusion, and the day after ECP. When cultured for 48 h, lymphocytes treated with ECP underwent accelerated apoptosis (tested as annexin V binding cells and as intracellular histone-associated DNA fragments) in comparison with lymphocytes from the other samples. This enhanced programmed cell death could not be prevented by IL-2. Immediately after isolation, there was no difference in Bcl-2 or bax expression among the four different samples, or in Fas and FasL mRNA. However, when cultured, lymphocytes treated with ECP showed a rapid downregulation of Bcl-2, an upregulation of bax with an increased bax/Bcl-2 ratio, a decrease in bcl-2 mRNA and an increase in Fas. No changes were detectable in lymphocytes from the other samples. IL-2 and TNF-alpha production was not significantly different among lymphocytes from the four samples. In conclusion, in patients affected by cGVHD, ECP induced apoptosis of lymphocytes with the involvement of both the Fas/FasL system and the Bcl-2 protein family.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0340-3696
pubmed:author
pubmed:issnType
Print
pubmed:volume
295
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
175-82
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12883827-Adult, pubmed-meshheading:12883827-Antigens, CD95, pubmed-meshheading:12883827-Apoptosis, pubmed-meshheading:12883827-Bone Marrow Transplantation, pubmed-meshheading:12883827-Cells, Cultured, pubmed-meshheading:12883827-Chronic Disease, pubmed-meshheading:12883827-Down-Regulation, pubmed-meshheading:12883827-Fas Ligand Protein, pubmed-meshheading:12883827-Female, pubmed-meshheading:12883827-Gene Expression, pubmed-meshheading:12883827-Graft vs Host Disease, pubmed-meshheading:12883827-Humans, pubmed-meshheading:12883827-Interleukin-2, pubmed-meshheading:12883827-Lymphocytes, pubmed-meshheading:12883827-Male, pubmed-meshheading:12883827-Membrane Glycoproteins, pubmed-meshheading:12883827-Photopheresis, pubmed-meshheading:12883827-Proto-Oncogene Proteins, pubmed-meshheading:12883827-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:12883827-Tumor Necrosis Factor-alpha, pubmed-meshheading:12883827-Up-Regulation, pubmed-meshheading:12883827-bcl-2-Associated X Protein
pubmed:year
2003
pubmed:articleTitle
ECP-treated lymphocytes of chronic graft-versus-host disease patients undergo apoptosis which involves both the Fas/FasL system and the Bcl-2 protein family.
pubmed:affiliation
Department of Internal Medicine and Immunological Sciences, University of Siena, 53100 Siena, Italy. cd28apo@hotmail.com
pubmed:publicationType
Journal Article