Rapamycin induces a caspase-independent cell death in human monocytes.
Am J Transplant
; 6(6): 1331-41, 2006 Jun.
Article
em En
| MEDLINE
| ID: mdl-16686757
ABSTRACT
The immunosuppressive activity of rapamycin (RAPA) and its efficacy as an anti-rejection agent in organ transplantation have been ascribed principally to its anti-proliferative effects on T cells, while the activity on monocytes is partially unknown. In vitro, RAPA reduced monocyte survival by inducing a caspase-independent cell death. RAPA-induced monocyte cell death (RAPA-CD) was impeded by activation of granulocyte macrophage-colony stimulating factor family receptors or toll-like receptor 4, and by exposure to inflammatory cytokines. In vivo, in patients who received RAPA monotherapy as part of pre-conditioning for islet transplantation, RAPA affected survival of myeloid lineage cells. In the peripheral blood, CD33(+) and CD14(+) cells decreased, whereas lymphocytes appeared unaffected. In the bone marrow, myeloid precursors such as CD15(+) and CD15(+)/CD16(+) were selectively and significantly decreased, but no major cytotoxic effects were observed. The RAPA-CD suggests a dependence of monocytes on mammalian target of RAPA pathways for nutrient usage, and this feature implies that RAPA could be selectively useful as a treatment to reduce monocytes or myeloid cells in conditions where these cells negatively affect patient, suggesting a potential anti-inflammatory action of this drug.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos
/
Monócitos
/
Morte Celular
/
Sirolimo
Limite:
Humans
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article