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Rapamycin Induces a Caspase‐Independent Cell Death in Human Monocytes
Author(s) -
Mercalli A.,
Sordi V.,
Ponzoni M.,
Maffi P.,
De Taddeo F.,
Gatti G.,
Servida P.,
Bernardi M.,
Bellio L.,
Bertuzzi F.,
Secchi A.,
Bonifacio E.,
Piemonti L.
Publication year - 2006
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2006.01332.x
Subject(s) - cd14 , monocyte , cd16 , myeloid , immunology , cytotoxic t cell , medicine , transplantation , cancer research , biology , immune system , in vitro , cd8 , biochemistry , cd3
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.