Severe Traumatic Injury Induces Phenotypic and Functional Changes of Neutrophils and Monocytes
Background: Severe traumatic injury has been associated with high susceptibility for the development of secondary complications caused by dysbalanced immune response. As the first line of the cellular immune response, neutrophils and monocytes recruited to the site of tissue damage and/or infection,...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/10/18/4139 |
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| author | Andrea Janicova Nils Becker Baolin Xu Marija Simic Laurens Noack Nils Wagner Andreas J. Müller Jessica Bertrand Ingo Marzi Borna Relja |
| author_facet | Andrea Janicova Nils Becker Baolin Xu Marija Simic Laurens Noack Nils Wagner Andreas J. Müller Jessica Bertrand Ingo Marzi Borna Relja |
| author_sort | Andrea Janicova |
| collection | DOAJ |
| description | Background: Severe traumatic injury has been associated with high susceptibility for the development of secondary complications caused by dysbalanced immune response. As the first line of the cellular immune response, neutrophils and monocytes recruited to the site of tissue damage and/or infection, are divided into three different subsets according to their CD16/CD62L and CD16/CD14 expression, respectively. Their differential functions have not yet been clearly understood. Thus, we evaluated the phenotypic changes of neutrophil and monocyte subsets among their functionality regarding oxidative burst and the phagocytic capacity in severely traumatized patients. Methods: Peripheral blood was withdrawn from severely injured trauma patients (TP; <i>n</i> = 15, ISS ≥ 16) within the first 12 h post-trauma and from healthy volunteers (HV; <i>n</i> = 15) and stimulated with fMLP and PMA. CD16<sup>dim</sup>CD62L<sup>bright</sup> (immature), CD16<sup>bright</sup>CD62L<sup>bright</sup> (mature) and CD16<sup>bright</sup>CD62L<sup>dim</sup> (CD62L<sup>low</sup>) neutrophil subsets and CD14<sup>bright</sup>CD16<sup>−</sup> (classical), CD14<sup>bright</sup>CD16<sup>+</sup> (intermediate) and CD14<sup>dim</sup>CD16<sup>+</sup> (non-classical) monocyte subsets of HV and TP were either directly analyzed by flow cytometry or the examined subsets of HV were sorted first by fluorescence-activated cell sorting and subsequently analyzed. Subset-specific generation of reactive oxygen species (ROS) and of <i>E. coli</i> bioparticle phagocytosis were evaluated. Results: In TP, the counts of immature neutrophils were significantly increased vs. HV. The numbers of mature and CD62L<sup>dim</sup> neutrophils remained unchanged but the production of ROS was significantly enhanced in TP vs. HV and the stimulation with fMLP significantly increased the generation of ROS in the mature and CD62L<sup>dim</sup> neutrophils of HV. The counts of phagocyting neutrophils did not change but the mean phagocytic capacity showed an increasing trend in TP. In TP, the monocytes shifted toward the intermediate phenotype, whereas the classical and non-classical monocytes became less abundant. ROS generation was significantly increased in all monocyte subsets in TP vs. HV and PMA stimulation significantly increased those level in both, HV and TP. However, the PMA-induced mean ROS generation was significantly lower in intermediate monocytes of TP vs. HV. Sorting of monocyte and neutrophil subsets revealed a significant increase of ROS and decrease of phagocytic capacity vs. whole blood analysis. Conclusions: Neutrophils and monocytes display a phenotypic shift following severe injury. The increased functional abnormalities of certain subsets may contribute to the dysbalanced immune response and attenuate the antimicrobial function and thus, may represent a potential therapeutic target. Further studies on isolated subsets are necessary for evaluation of their physiological role after severe traumatic injury. |
| first_indexed | 2024-03-10T07:33:56Z |
| format | Article |
| id | doaj.art-808d70f7dc94417a88af3f2e797e0123 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T07:33:56Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-808d70f7dc94417a88af3f2e797e01232023-11-22T13:40:04ZengMDPI AGJournal of Clinical Medicine2077-03832021-09-011018413910.3390/jcm10184139Severe Traumatic Injury Induces Phenotypic and Functional Changes of Neutrophils and MonocytesAndrea Janicova0Nils Becker1Baolin Xu2Marija Simic3Laurens Noack4Nils Wagner5Andreas J. Müller6Jessica Bertrand7Ingo Marzi8Borna Relja9Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University Magdeburg, Leipziger Straße 44, 39120 Magdeburg, GermanyExperimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University Magdeburg, Leipziger Straße 44, 39120 Magdeburg, GermanyExperimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University Magdeburg, Leipziger Straße 44, 39120 Magdeburg, GermanyExperimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University Magdeburg, Leipziger Straße 44, 39120 Magdeburg, GermanyExperimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University Magdeburg, Leipziger Straße 44, 39120 Magdeburg, GermanyDepartment of Trauma, Hand and Reconstructive Surgery, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, GermanyInstitute of Molecular and Clinical Immunology, Health Campus Immunology Infectiology and Inflammation, Otto-von-Guericke-University Magdeburg, Leipziger Straße 44, 39120 Magdeburg, GermanyDepartment of Orthopaedic Surgery, Otto-von-Guericke University Magdeburg, Leipziger Straße 44, 39120 Magdeburg, GermanyDepartment of Trauma, Hand and Reconstructive Surgery, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, GermanyExperimental Radiology, Department of Radiology and Nuclear Medicine, Otto-von-Guericke-University Magdeburg, Leipziger Straße 44, 39120 Magdeburg, GermanyBackground: Severe traumatic injury has been associated with high susceptibility for the development of secondary complications caused by dysbalanced immune response. As the first line of the cellular immune response, neutrophils and monocytes recruited to the site of tissue damage and/or infection, are divided into three different subsets according to their CD16/CD62L and CD16/CD14 expression, respectively. Their differential functions have not yet been clearly understood. Thus, we evaluated the phenotypic changes of neutrophil and monocyte subsets among their functionality regarding oxidative burst and the phagocytic capacity in severely traumatized patients. Methods: Peripheral blood was withdrawn from severely injured trauma patients (TP; <i>n</i> = 15, ISS ≥ 16) within the first 12 h post-trauma and from healthy volunteers (HV; <i>n</i> = 15) and stimulated with fMLP and PMA. CD16<sup>dim</sup>CD62L<sup>bright</sup> (immature), CD16<sup>bright</sup>CD62L<sup>bright</sup> (mature) and CD16<sup>bright</sup>CD62L<sup>dim</sup> (CD62L<sup>low</sup>) neutrophil subsets and CD14<sup>bright</sup>CD16<sup>−</sup> (classical), CD14<sup>bright</sup>CD16<sup>+</sup> (intermediate) and CD14<sup>dim</sup>CD16<sup>+</sup> (non-classical) monocyte subsets of HV and TP were either directly analyzed by flow cytometry or the examined subsets of HV were sorted first by fluorescence-activated cell sorting and subsequently analyzed. Subset-specific generation of reactive oxygen species (ROS) and of <i>E. coli</i> bioparticle phagocytosis were evaluated. Results: In TP, the counts of immature neutrophils were significantly increased vs. HV. The numbers of mature and CD62L<sup>dim</sup> neutrophils remained unchanged but the production of ROS was significantly enhanced in TP vs. HV and the stimulation with fMLP significantly increased the generation of ROS in the mature and CD62L<sup>dim</sup> neutrophils of HV. The counts of phagocyting neutrophils did not change but the mean phagocytic capacity showed an increasing trend in TP. In TP, the monocytes shifted toward the intermediate phenotype, whereas the classical and non-classical monocytes became less abundant. ROS generation was significantly increased in all monocyte subsets in TP vs. HV and PMA stimulation significantly increased those level in both, HV and TP. However, the PMA-induced mean ROS generation was significantly lower in intermediate monocytes of TP vs. HV. Sorting of monocyte and neutrophil subsets revealed a significant increase of ROS and decrease of phagocytic capacity vs. whole blood analysis. Conclusions: Neutrophils and monocytes display a phenotypic shift following severe injury. The increased functional abnormalities of certain subsets may contribute to the dysbalanced immune response and attenuate the antimicrobial function and thus, may represent a potential therapeutic target. Further studies on isolated subsets are necessary for evaluation of their physiological role after severe traumatic injury.https://www.mdpi.com/2077-0383/10/18/4139traumatic injuryreactive oxygen speciesphagocytosisCD14CD16CD62L |
| spellingShingle | Andrea Janicova Nils Becker Baolin Xu Marija Simic Laurens Noack Nils Wagner Andreas J. Müller Jessica Bertrand Ingo Marzi Borna Relja Severe Traumatic Injury Induces Phenotypic and Functional Changes of Neutrophils and Monocytes Journal of Clinical Medicine traumatic injury reactive oxygen species phagocytosis CD14 CD16 CD62L |
| title | Severe Traumatic Injury Induces Phenotypic and Functional Changes of Neutrophils and Monocytes |
| title_full | Severe Traumatic Injury Induces Phenotypic and Functional Changes of Neutrophils and Monocytes |
| title_fullStr | Severe Traumatic Injury Induces Phenotypic and Functional Changes of Neutrophils and Monocytes |
| title_full_unstemmed | Severe Traumatic Injury Induces Phenotypic and Functional Changes of Neutrophils and Monocytes |
| title_short | Severe Traumatic Injury Induces Phenotypic and Functional Changes of Neutrophils and Monocytes |
| title_sort | severe traumatic injury induces phenotypic and functional changes of neutrophils and monocytes |
| topic | traumatic injury reactive oxygen species phagocytosis CD14 CD16 CD62L |
| url | https://www.mdpi.com/2077-0383/10/18/4139 |
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