Impact of BH3-mimetics on Human and Mouse Blood Leukocytes: A Comparative Study
| Autor: | Ramona Reinhart, Sofia Bachmann, Lionel Rohner, Joseena Iype, Thomas Kaufmann, Michaela Fux |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Programmed cell death
lcsh:Medicine 610 Medicine & health Antineoplastic Agents Biology Article Flow cytometry Mice Bridged Bicyclo Compounds Biomimetics Proto-Oncogene Proteins Cell death and immune response Leukocytes medicine Animals Humans lcsh:Science Sulfonamides Bh3 mimetics Multidisciplinary medicine.diagnostic_test Immune cell death lcsh:R Wild type mice Bridged Bicyclo Compounds Heterocyclic Peptide Fragments Cancer treatment Mice Inbred C57BL Proto-Oncogene Proteins c-bcl-2 Immunology lcsh:Q biological phenomena cell phenomena and immunity Function (biology) Ex vivo |
| Zdroj: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-8 (2020) Rohner, Lionel; Reinhart, Ramona; Iype, Joseena; Bachmann, Sofia; Kaufmann, Thomas; Fux, Michaela (2020). Impact of BH3-mimetics on Human and Mouse Blood Leukocytes: A Comparative Study. Scientific reports, 10(1), p. 222. Springer Nature 10.1038/s41598-019-57000-x |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-019-57000-x |
| Popis: | BH3-mimetics are small molecule inhibitors that neutralize the function of anti-apoptotic BCL-2 family members. BH3-mimetics have recently gained a lot of popularity in oncology because of their success in cancer treatment. However, BH3-mimetics might have a broader clinical application. Here, we established an ex vivo flow cytometric assay allowing the comparison of the impact of BH3-mimetics (ABT-199, ABT-263, WEHI-539, and S63845) on leukocyte populations of both, healthy human subjects and C57BL/6 J wild type mice. BH3-mimetics were added to freshly drawn blood that was diluted 1/2 in cell medium, and BH3-mimetics-mediated impact on leukocyte count was assessed by flow cytometry. Our results demonstrate that responses towards 1μM of BH3-mimetics can be identical as well as considerably different in leukocytes of humans and mice. For instance, the inhibition of BCL-2 by ABT-199 caused cell death in all types of lymphocytes in mice but was exclusively specific for B cells in humans. Moreover, inhibition of BCL-XL by WEHI-539 affected solely mouse leukocytes while targeting MCL-1 by S63845 resulted in efficient induction of cell death in human neutrophils but not in their mouse counterparts. Our ex vivo assay enables initial identification of analogies and differences between human and mouse leukocytes in response towards BH3-mimetics. |
| Databáze: | OpenAIRE |
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