Radical-Generating Activity, Phagocytosis, and Mechanical Properties of Four Phenotypes of Human Macrophages
Macrophages are the major players and orchestrators of inflammatory response. Expressed proteins and secreted cytokines have been well studied for two polar macrophage phenotypes—pro-inflammatory M1 and anti-inflammatory regenerative M2, but little is known about how the polarization modulates macro...
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MDPI AG
2024-02-01
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| Series: | International Journal of Molecular Sciences |
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| author | Shakir K. Suleimanov Yuri M. Efremov Timofey O. Klyucherev Emin L. Salimov Aligeydar A. Ragimov Peter S. Timashev Irina I. Vlasova |
| author_facet | Shakir K. Suleimanov Yuri M. Efremov Timofey O. Klyucherev Emin L. Salimov Aligeydar A. Ragimov Peter S. Timashev Irina I. Vlasova |
| author_sort | Shakir K. Suleimanov |
| collection | DOAJ |
| description | Macrophages are the major players and orchestrators of inflammatory response. Expressed proteins and secreted cytokines have been well studied for two polar macrophage phenotypes—pro-inflammatory M1 and anti-inflammatory regenerative M2, but little is known about how the polarization modulates macrophage functions. In this study, we used biochemical and biophysical methods to compare the functional activity and mechanical properties of activated human macrophages differentiated from monocyte with GM-CSF (M0_GM) and M-CSF (M0_M) and polarized into M1 and M2 phenotypes, respectively. Unlike GM-CSF, which generates dormant cells with low activity, M-CSF confers functional activity on macrophages. M0_M and M2 macrophages had very similar functional characteristics—high reactive oxygen species (ROS) production level, and higher phagocytosis and survival compared to M1, while M1 macrophages showed the highest radical-generating activity but the lowest phagocytosis and survival among all phenotypes. All phenotypes decreased their height upon activation, but only M1 and M2 cells increased in stiffness, which can indicate a decrease in the migration ability of these cells and changes in their interactions with other cells. Our results demonstrated that while mechanical properties differ between M0 and polarized cells, all four phenotypes of monocyte-derived macrophages differ in their functional activities, namely in cytokine secretion, ROS production, and phagocytosis. Within the broad continuum of human macrophages obtained in experimental models and existing in vivo, there is a diversity of phenotypes with varying combinations of both markers and functional activities. |
| first_indexed | 2024-03-08T03:54:18Z |
| format | Article |
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| language | English |
| last_indexed | 2024-03-08T03:54:18Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-12ba479c35d643b7a5fdce5ac35745b52024-02-09T15:14:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-02-01253186010.3390/ijms25031860Radical-Generating Activity, Phagocytosis, and Mechanical Properties of Four Phenotypes of Human MacrophagesShakir K. Suleimanov0Yuri M. Efremov1Timofey O. Klyucherev2Emin L. Salimov3Aligeydar A. Ragimov4Peter S. Timashev5Irina I. Vlasova6Institute for Regenerative Medicine, I. M. Sechenov First Moscow State Medical University, 119991 Moscow, RussiaInstitute for Regenerative Medicine, I. M. Sechenov First Moscow State Medical University, 119991 Moscow, RussiaInstitute for Regenerative Medicine, I. M. Sechenov First Moscow State Medical University, 119991 Moscow, RussiaLaboratory Blood Transfusion Complex, I. M. Sechenov First Moscow State Medical University, 119991 Moscow, RussiaLaboratory Blood Transfusion Complex, I. M. Sechenov First Moscow State Medical University, 119991 Moscow, RussiaInstitute for Regenerative Medicine, I. M. Sechenov First Moscow State Medical University, 119991 Moscow, RussiaInstitute for Regenerative Medicine, I. M. Sechenov First Moscow State Medical University, 119991 Moscow, RussiaMacrophages are the major players and orchestrators of inflammatory response. Expressed proteins and secreted cytokines have been well studied for two polar macrophage phenotypes—pro-inflammatory M1 and anti-inflammatory regenerative M2, but little is known about how the polarization modulates macrophage functions. In this study, we used biochemical and biophysical methods to compare the functional activity and mechanical properties of activated human macrophages differentiated from monocyte with GM-CSF (M0_GM) and M-CSF (M0_M) and polarized into M1 and M2 phenotypes, respectively. Unlike GM-CSF, which generates dormant cells with low activity, M-CSF confers functional activity on macrophages. M0_M and M2 macrophages had very similar functional characteristics—high reactive oxygen species (ROS) production level, and higher phagocytosis and survival compared to M1, while M1 macrophages showed the highest radical-generating activity but the lowest phagocytosis and survival among all phenotypes. All phenotypes decreased their height upon activation, but only M1 and M2 cells increased in stiffness, which can indicate a decrease in the migration ability of these cells and changes in their interactions with other cells. Our results demonstrated that while mechanical properties differ between M0 and polarized cells, all four phenotypes of monocyte-derived macrophages differ in their functional activities, namely in cytokine secretion, ROS production, and phagocytosis. Within the broad continuum of human macrophages obtained in experimental models and existing in vivo, there is a diversity of phenotypes with varying combinations of both markers and functional activities.https://www.mdpi.com/1422-0067/25/3/1860myeloid-derived macrophagesreactive oxygen speciesredox activityphagocytosisYoung’s modulus |
| spellingShingle | Shakir K. Suleimanov Yuri M. Efremov Timofey O. Klyucherev Emin L. Salimov Aligeydar A. Ragimov Peter S. Timashev Irina I. Vlasova Radical-Generating Activity, Phagocytosis, and Mechanical Properties of Four Phenotypes of Human Macrophages International Journal of Molecular Sciences myeloid-derived macrophages reactive oxygen species redox activity phagocytosis Young’s modulus |
| title | Radical-Generating Activity, Phagocytosis, and Mechanical Properties of Four Phenotypes of Human Macrophages |
| title_full | Radical-Generating Activity, Phagocytosis, and Mechanical Properties of Four Phenotypes of Human Macrophages |
| title_fullStr | Radical-Generating Activity, Phagocytosis, and Mechanical Properties of Four Phenotypes of Human Macrophages |
| title_full_unstemmed | Radical-Generating Activity, Phagocytosis, and Mechanical Properties of Four Phenotypes of Human Macrophages |
| title_short | Radical-Generating Activity, Phagocytosis, and Mechanical Properties of Four Phenotypes of Human Macrophages |
| title_sort | radical generating activity phagocytosis and mechanical properties of four phenotypes of human macrophages |
| topic | myeloid-derived macrophages reactive oxygen species redox activity phagocytosis Young’s modulus |
| url | https://www.mdpi.com/1422-0067/25/3/1860 |
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