Acquired immunological imbalance after surgery with cardiopulmonary bypass due to epigenetic over-activation of PU.1/M-CSF
Abstract Background It has been shown that severe insult to the immune system may trigger prolonged macrophage characteristics associated with excessive release of monocyte colony stimulating factor (M-CSF). However, it is unclear how persistent is the macrophage-like characteristics in circulating...
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| Format: | Article |
| Language: | English |
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BMC
2018-05-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | http://link.springer.com/article/10.1186/s12967-018-1518-3 |
| _version_ | 1819072727610294272 |
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| author | Krzysztof Laudanski Mateusz Zawadka Jacek Polosak Jaymin Modi Matthew DiMeglio Jacob Gutsche Wilson Y. Szeto Monika Puzianowska-Kuznicka |
| author_facet | Krzysztof Laudanski Mateusz Zawadka Jacek Polosak Jaymin Modi Matthew DiMeglio Jacob Gutsche Wilson Y. Szeto Monika Puzianowska-Kuznicka |
| author_sort | Krzysztof Laudanski |
| collection | DOAJ |
| description | Abstract Background It has been shown that severe insult to the immune system may trigger prolonged macrophage characteristics associated with excessive release of monocyte colony stimulating factor (M-CSF). However, it is unclear how persistent is the macrophage-like characteristics in circulating monocytes (MO). In this study, 20 patients who underwent non-emergent cardiopulmonary bypass had their monocytes characterized before surgery and 3 months after surgery. Methods We assessed the macrophage characteristics of MO using cytokine production, surface marker expression, an ability to stimulate T cells, and methylation of the promoter region of the gene encoding PU.1, a critical component to M-CSF production. MO function as well as activation and differentiation potential were longitudinally assessed. Results At 3 months after cardiopulmonary bypass, monocytes exhibited increased expression of MRP8, transforming growth factor-β/latency-associated peptide, suppressor of cytokine signaling 3 while phagocytic properties were increased. Concomitantly, we observed a decreased expression of CD86, a decreased ability to form regulatory dendritic cells, and a diminished ability to stimulate T cells. These characteristics were accompanied by a persistent increase in the secretion of M-CSF, over-activation of PU.1, and decreased methylation of the PU.1 promoter region. Serum levels of C-reactive protein and anti-cytomegalovirus IgG antibody titers were also elevated in some patients at 3 months after surgery. Conclusions We concluded that at 3 months after cardiopulmonary bypass, monocytes continued to express a new macrophage-like milieu that was associated with the persistent activation of the PU.1/M-CSF pathway. |
| first_indexed | 2024-12-21T17:42:19Z |
| format | Article |
| id | doaj.art-3b96f1a0692348e0b95fe37cf009a03b |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-21T17:42:19Z |
| publishDate | 2018-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-3b96f1a0692348e0b95fe37cf009a03b2022-12-21T18:55:36ZengBMCJournal of Translational Medicine1479-58762018-05-0116111310.1186/s12967-018-1518-3Acquired immunological imbalance after surgery with cardiopulmonary bypass due to epigenetic over-activation of PU.1/M-CSFKrzysztof Laudanski0Mateusz Zawadka1Jacek Polosak2Jaymin Modi3Matthew DiMeglio4Jacob Gutsche5Wilson Y. Szeto6Monika Puzianowska-Kuznicka7Department of Anesthesiology, University of PennsylvaniaDepartment of Anesthesiology, Medical University of WarsawDepartment of Human Epigenetics, Mossakowski Medical Research CentrePhiladelphia College of Osteopathic MedicinePhiladelphia College of Osteopathic MedicineDepartment of Anesthesiology, University of PennsylvaniaDivision of Cardiovascular Surgery, University of PennsylvaniaDepartment of Human Epigenetics, Mossakowski Medical Research CentreAbstract Background It has been shown that severe insult to the immune system may trigger prolonged macrophage characteristics associated with excessive release of monocyte colony stimulating factor (M-CSF). However, it is unclear how persistent is the macrophage-like characteristics in circulating monocytes (MO). In this study, 20 patients who underwent non-emergent cardiopulmonary bypass had their monocytes characterized before surgery and 3 months after surgery. Methods We assessed the macrophage characteristics of MO using cytokine production, surface marker expression, an ability to stimulate T cells, and methylation of the promoter region of the gene encoding PU.1, a critical component to M-CSF production. MO function as well as activation and differentiation potential were longitudinally assessed. Results At 3 months after cardiopulmonary bypass, monocytes exhibited increased expression of MRP8, transforming growth factor-β/latency-associated peptide, suppressor of cytokine signaling 3 while phagocytic properties were increased. Concomitantly, we observed a decreased expression of CD86, a decreased ability to form regulatory dendritic cells, and a diminished ability to stimulate T cells. These characteristics were accompanied by a persistent increase in the secretion of M-CSF, over-activation of PU.1, and decreased methylation of the PU.1 promoter region. Serum levels of C-reactive protein and anti-cytomegalovirus IgG antibody titers were also elevated in some patients at 3 months after surgery. Conclusions We concluded that at 3 months after cardiopulmonary bypass, monocytes continued to express a new macrophage-like milieu that was associated with the persistent activation of the PU.1/M-CSF pathway.http://link.springer.com/article/10.1186/s12967-018-1518-3EpigeneticsCardiopulmonary bypassPU.1MonocytesGranulocyte colony stimulating factor |
| spellingShingle | Krzysztof Laudanski Mateusz Zawadka Jacek Polosak Jaymin Modi Matthew DiMeglio Jacob Gutsche Wilson Y. Szeto Monika Puzianowska-Kuznicka Acquired immunological imbalance after surgery with cardiopulmonary bypass due to epigenetic over-activation of PU.1/M-CSF Journal of Translational Medicine Epigenetics Cardiopulmonary bypass PU.1 Monocytes Granulocyte colony stimulating factor |
| title | Acquired immunological imbalance after surgery with cardiopulmonary bypass due to epigenetic over-activation of PU.1/M-CSF |
| title_full | Acquired immunological imbalance after surgery with cardiopulmonary bypass due to epigenetic over-activation of PU.1/M-CSF |
| title_fullStr | Acquired immunological imbalance after surgery with cardiopulmonary bypass due to epigenetic over-activation of PU.1/M-CSF |
| title_full_unstemmed | Acquired immunological imbalance after surgery with cardiopulmonary bypass due to epigenetic over-activation of PU.1/M-CSF |
| title_short | Acquired immunological imbalance after surgery with cardiopulmonary bypass due to epigenetic over-activation of PU.1/M-CSF |
| title_sort | acquired immunological imbalance after surgery with cardiopulmonary bypass due to epigenetic over activation of pu 1 m csf |
| topic | Epigenetics Cardiopulmonary bypass PU.1 Monocytes Granulocyte colony stimulating factor |
| url | http://link.springer.com/article/10.1186/s12967-018-1518-3 |
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