Club Cell Protein 16 Attenuates CD16brightCD62dim Immunosuppressive Neutrophils in Damaged Tissue upon Posttraumatic Sepsis-Induced Lung Injury
Background. Recently, identification of immunosuppressive polymorphonuclear leukocytes (PMNL) that were traditionally described as proinflammatory cells emerged in the field of posttraumatic immunity. To understand their local and remote distribution after trauma, PMNL-subsets and the impact of immu...
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Wiley
2021-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2021/6647753 |
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| author | Nils Becker Philipp Störmann Andrea Janicova Kernt Köhler Klemens Horst Ildiko Rita Dunay Claudia Neunaber Ingo Marzi Jan Tilmann Vollrath Borna Relja |
| author_facet | Nils Becker Philipp Störmann Andrea Janicova Kernt Köhler Klemens Horst Ildiko Rita Dunay Claudia Neunaber Ingo Marzi Jan Tilmann Vollrath Borna Relja |
| author_sort | Nils Becker |
| collection | DOAJ |
| description | Background. Recently, identification of immunosuppressive polymorphonuclear leukocytes (PMNL) that were traditionally described as proinflammatory cells emerged in the field of posttraumatic immunity. To understand their local and remote distribution after trauma, PMNL-subsets and the impact of immunomodulatory Club Cell protein (CC)16 that correlates with pulmonary complications were assessed. Methods. C57BL/6N mice were divided into three groups, receiving isolated blunt chest trauma (TxT), undergoing TxT followed by cecal ligation and puncture (CLP, TxT+CLP) after 24 h, or sham undergoing analgosedation (n=18/group). Further, each group was subdivided into three groups receiving either no treatment (ctrl) or intratracheal neutralization of CC16 by application of anti-CC16-antibody or application of an unspecific IgG control antibody (n=6/group). Treatment was set at the time point after TxT. Analyses followed 6 h post-CLP. PMNL were characterized via expression of CD11b, CD16, CD45, CD62L, and Ly6G by flow cytometry in bone marrow (BM), blood, spleen, lung, liver, and bronchoalveolar and peritoneal lavage fluid (BALF and PL). Apoptosis was assessed by activated (cleaved) caspase-3. Results from untreated ctrl and IgG-treated mice were statistically comparable between all corresponding sham, TxT, and TxT+CLP groups. Results. Immature (CD16dimCD62Lbright) PMNL increased significantly in BM, circulation, and spleen after TxT vs. sham and were significantly attenuated in the lungs, BALF, PL, and liver. Classical-shaped (CD16brightCD62Lbright) PMNL increased after TxT vs. sham in peripheral tissue and were significantly attenuated in circulation, proposing a trauma-induced migration of mature or peripheral differentiation of circulating immature PMNL. Immunosuppressive (CD16brightCD62Ldim) PMNL decreased significantly in the lungs and spleen, while they systemically increased after TxT vs. sham. CLP in the TxT+CLP group reduced immunosuppressive PMNL in PL and increased their circulatory rate vs. isolated TxT, showing local reduction in affected tissue and their increase in nonaffected tissue. CC16 neutralization enhanced the fraction of immunosuppressive PMNL following TxT vs. sham and decreased caspase-3 in the lungs post-CLP in the TxT+CLP group, while apoptotic cells in the liver diminished post-TxT. Posttraumatic CC16 neutralization promotes the subset of immunosuppressive PMNL and antagonizes their posttraumatic distribution. Conclusion. Since CC16 affects both the distribution of PMNL subsets and apoptosis in tissues after trauma, it may constitute as a novel target to beneficially shape the posttraumatic tissue microenvironment and homeostasis to improving outcomes. |
| format | Article |
| id | doaj-art-15bd260b53f741e99a983195e52391f1 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
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| series | Journal of Immunology Research |
| spelling | doaj-art-15bd260b53f741e99a983195e52391f12025-02-03T01:10:53ZengWileyJournal of Immunology Research2314-88612314-71562021-01-01202110.1155/2021/66477536647753Club Cell Protein 16 Attenuates CD16brightCD62dim Immunosuppressive Neutrophils in Damaged Tissue upon Posttraumatic Sepsis-Induced Lung InjuryNils Becker0Philipp Störmann1Andrea Janicova2Kernt Köhler3Klemens Horst4Ildiko Rita Dunay5Claudia Neunaber6Ingo Marzi7Jan Tilmann Vollrath8Borna Relja9Experimental Radiology, Department of Radiology and Nuclear Medicine, Otto von Guericke University, Magdeburg, GermanyDepartment of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, GermanyExperimental Radiology, Department of Radiology and Nuclear Medicine, Otto von Guericke University, Magdeburg, GermanyInstitute of Veterinary Pathology, Justus Liebig University Giessen, Giessen, GermanyDepartment of Trauma Surgery, Hospital of the RWTH University, Aachen, GermanyInstitute of Inflammation and Neurodegeneration, Otto von Guericke University, Magdeburg, GermanyTrauma Department, Hannover Medical School, Hannover, GermanyDepartment of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, GermanyDepartment of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, GermanyExperimental Radiology, Department of Radiology and Nuclear Medicine, Otto von Guericke University, Magdeburg, GermanyBackground. Recently, identification of immunosuppressive polymorphonuclear leukocytes (PMNL) that were traditionally described as proinflammatory cells emerged in the field of posttraumatic immunity. To understand their local and remote distribution after trauma, PMNL-subsets and the impact of immunomodulatory Club Cell protein (CC)16 that correlates with pulmonary complications were assessed. Methods. C57BL/6N mice were divided into three groups, receiving isolated blunt chest trauma (TxT), undergoing TxT followed by cecal ligation and puncture (CLP, TxT+CLP) after 24 h, or sham undergoing analgosedation (n=18/group). Further, each group was subdivided into three groups receiving either no treatment (ctrl) or intratracheal neutralization of CC16 by application of anti-CC16-antibody or application of an unspecific IgG control antibody (n=6/group). Treatment was set at the time point after TxT. Analyses followed 6 h post-CLP. PMNL were characterized via expression of CD11b, CD16, CD45, CD62L, and Ly6G by flow cytometry in bone marrow (BM), blood, spleen, lung, liver, and bronchoalveolar and peritoneal lavage fluid (BALF and PL). Apoptosis was assessed by activated (cleaved) caspase-3. Results from untreated ctrl and IgG-treated mice were statistically comparable between all corresponding sham, TxT, and TxT+CLP groups. Results. Immature (CD16dimCD62Lbright) PMNL increased significantly in BM, circulation, and spleen after TxT vs. sham and were significantly attenuated in the lungs, BALF, PL, and liver. Classical-shaped (CD16brightCD62Lbright) PMNL increased after TxT vs. sham in peripheral tissue and were significantly attenuated in circulation, proposing a trauma-induced migration of mature or peripheral differentiation of circulating immature PMNL. Immunosuppressive (CD16brightCD62Ldim) PMNL decreased significantly in the lungs and spleen, while they systemically increased after TxT vs. sham. CLP in the TxT+CLP group reduced immunosuppressive PMNL in PL and increased their circulatory rate vs. isolated TxT, showing local reduction in affected tissue and their increase in nonaffected tissue. CC16 neutralization enhanced the fraction of immunosuppressive PMNL following TxT vs. sham and decreased caspase-3 in the lungs post-CLP in the TxT+CLP group, while apoptotic cells in the liver diminished post-TxT. Posttraumatic CC16 neutralization promotes the subset of immunosuppressive PMNL and antagonizes their posttraumatic distribution. Conclusion. Since CC16 affects both the distribution of PMNL subsets and apoptosis in tissues after trauma, it may constitute as a novel target to beneficially shape the posttraumatic tissue microenvironment and homeostasis to improving outcomes.http://dx.doi.org/10.1155/2021/6647753 |
| spellingShingle | Nils Becker Philipp Störmann Andrea Janicova Kernt Köhler Klemens Horst Ildiko Rita Dunay Claudia Neunaber Ingo Marzi Jan Tilmann Vollrath Borna Relja Club Cell Protein 16 Attenuates CD16brightCD62dim Immunosuppressive Neutrophils in Damaged Tissue upon Posttraumatic Sepsis-Induced Lung Injury Journal of Immunology Research |
| title | Club Cell Protein 16 Attenuates CD16brightCD62dim Immunosuppressive Neutrophils in Damaged Tissue upon Posttraumatic Sepsis-Induced Lung Injury |
| title_full | Club Cell Protein 16 Attenuates CD16brightCD62dim Immunosuppressive Neutrophils in Damaged Tissue upon Posttraumatic Sepsis-Induced Lung Injury |
| title_fullStr | Club Cell Protein 16 Attenuates CD16brightCD62dim Immunosuppressive Neutrophils in Damaged Tissue upon Posttraumatic Sepsis-Induced Lung Injury |
| title_full_unstemmed | Club Cell Protein 16 Attenuates CD16brightCD62dim Immunosuppressive Neutrophils in Damaged Tissue upon Posttraumatic Sepsis-Induced Lung Injury |
| title_short | Club Cell Protein 16 Attenuates CD16brightCD62dim Immunosuppressive Neutrophils in Damaged Tissue upon Posttraumatic Sepsis-Induced Lung Injury |
| title_sort | club cell protein 16 attenuates cd16brightcd62dim immunosuppressive neutrophils in damaged tissue upon posttraumatic sepsis induced lung injury |
| url | http://dx.doi.org/10.1155/2021/6647753 |
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