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Rapamycin Induces a Caspase-Independent Cell Death in Human Monocytes
- Source :
- American Journal of Transplantation; June 2006, Vol. 6 Issue: 6 p1331-1341, 11p
- Publication Year :
- 2006
-
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.
Details
- Language :
- English
- ISSN :
- 16006135 and 16006143
- Volume :
- 6
- Issue :
- 6
- Database :
- Supplemental Index
- Journal :
- American Journal of Transplantation
- Publication Type :
- Periodical
- Accession number :
- ejs8913325
- Full Text :
- https://doi.org/10.1111/j.1600-6143.2006.01332.x