Rapamycin but not FK506 inhibits the proliferation of mononuclear phagocytes induced by colony-stimulating factors
Autor: | M. H. Cooper, Stephen H. Gregory, Edward J. Wing, Thomas E. Starzl |
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Rok vydání: | 1994 |
Předmět: |
medicine.medical_specialty
Phagocyte T-Lymphocytes Population Tetrazolium Salts Bone Marrow Cells Cell Count Polyenes Pharmacology Biology Granulocyte Lymphocyte Activation Tritium Tacrolimus Article Mice Colony-Stimulating Factors Internal medicine medicine Concanavalin A Macrophage Animals education Sirolimus Transplantation education.field_of_study Phagocytes Monocyte Mononuclear phagocyte system Colony-stimulating factor Mice Inbred C57BL Thiazoles Granulocyte macrophage colony-stimulating factor medicine.anatomical_structure Endocrinology Culture Media Conditioned Cyclosporine Female Cell Division Spleen medicine.drug Thymidine |
Zdroj: | Transplantation. 57(3) |
ISSN: | 0041-1337 |
Popis: | FK506, CsA, and rapamycin are potent inhibitors of T lymphocyte activation; relatively little is known of their effects on cells of the monocyte/macrophage lineage. Studies were undertaken to determine the effects of these drugs on the proliferative response of bone marrow-derived mononuclear phagocytes (BMMP) to CSFs. Rapamycin inhibited the proliferation of BMMP cultured in the presence of 10% L cell-conditioned medium, used as a source of macrophage CSF. The inhibition by rapamycin was dose dependent and apparent at concentrations of 0.1 nM or greater. In a similar fashion, rapamycin inhibited the proliferation of BMMP stimulated by the recombinant forms of murine IL-3 and murine granulocyte-macrophage CSF, and human macrophage CSF. In contrast, neither FK506 nor CsA at concentrations as high as 1000 nM diminished the proliferation of BMMP cultured under identical conditions. FK506, but not CsA, blocked the inhibitory effects of rapamycin on the response of BMMP to CSFs. In summary, these data indicate that rapamycin inhibits the proliferation of BMMP in response to CSFs. These results imply that patients receiving rapamycin, but not FK506 or CsA, may have an impaired ability to generate a functional mononuclear phagocyte population. |
Databáze: | OpenAIRE |
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