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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.
Laudanski, K., Zawadka, M., Polosak, J., Modi, J., DiMeglio, M., Gutsche, J., … Puzianowska-Kuznicka, M. (2018). Acquired immunological imbalance after surgery with cardiopulmonary bypass due to epigenetic over-activation of PU.1/M-CSF. Journal of Translational Medicine, 16(1). https://doi.org/10.1186/s12967-018-1518-3