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Club cell protein 16 in sera from trauma patients modulates neutrophil migration and functionality via CXCR1 and CXCR2
BACKGROUND: Club Cell protein (CC)16 correlates with lung injury and respiratory complications, which are in part triggered by polymorphonuclear leukocytes (PMNL) in severely traumatized patients (TP). CC16 exerts anti-inflammatory and immunosuppressive effects, however, its influence on PMNL functi...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822417/ https://www.ncbi.nlm.nih.gov/pubmed/31666007 http://dx.doi.org/10.1186/s10020-019-0115-0 |
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author | Xu, Baolin Janicova, Andrea Vollrath, Jan Tilmann Störmann, Philipp Martin, Lukas Marzi, Ingo Wutzler, Sebastian Hildebrand, Frank Ehnert, Sabrina Relja, Borna |
author_facet | Xu, Baolin Janicova, Andrea Vollrath, Jan Tilmann Störmann, Philipp Martin, Lukas Marzi, Ingo Wutzler, Sebastian Hildebrand, Frank Ehnert, Sabrina Relja, Borna |
author_sort | Xu, Baolin |
collection | PubMed |
description | BACKGROUND: Club Cell protein (CC)16 correlates with lung injury and respiratory complications, which are in part triggered by polymorphonuclear leukocytes (PMNL) in severely traumatized patients (TP). CC16 exerts anti-inflammatory and immunosuppressive effects, however, its influence on PMNL functions after trauma is unknown. Here, we evaluated whether CC16 present in sera from TP could modify the biological functions of PMNL. METHODS: Sera from 16 severely injured TP without pneumonia (no P, n = 8) or with pneumonia (P, n = 8) were collected at admission to emergency department (ED) and 1 day prior pneumonia and pre-incubated with or without anti-CC16 antibody for CC16 neutralization. Samples from the equal post-injury days in the corresponding no P group were used. Neutrophils were isolated from healthy volunteers (HV, n = 5) and incubated with 20% of the serum medium from TP, respectively. In PMNL, CD62L, CD11b/CD18 and CD31 expression, migratory capacity, phagocytosis rate, oxidative burst and apoptosis were investigated. In isolated PMNL, CXCR1 and CXCR2 were neutralized before stimulation with CC16, and oxidative burst, phagocytosis and apoptosis were analyzed in neutrophils and their subsets. RESULTS: Serum from the P group enhanced significantly PMNL migration compared to no P group, while CC16-neutralization further increased the migratory rate of PMNL in both groups. CC16-neutralization increased significantly the expression of CD62L in the P group at ED. Oxidative burst was significantly increased in the P group vs. no P during the study period. CC16 seemed to have no influence on oxidative burst and phagocytosis in TP. However, in a more controlled study design, CC16 induced a significant increase of oxidative burst and a decrease of apoptosis of CD16(+) granulocytes. These effects were markedly observed in mature CD16(bright)CD62L(bright) and immune suppressive CD16(bright)CD62L(dim) neutrophils. In mature subset, CXCR1 and CXCR2 neutralization diminished CC16-induced effects. CONCLUSIONS: CC16 in sera from multiply traumatized patients, notably of those with pneumonia, has significant effects on PMNL. The results suggest an association of CC16 with CXCR1 and CXCR2. Our data suggest that CC16 reduces the migratory capacity of PMNL and thus modulates their function in patients with respiratory complications after trauma. |
format | Online Article Text |
id | pubmed-6822417 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-68224172019-11-07 Club cell protein 16 in sera from trauma patients modulates neutrophil migration and functionality via CXCR1 and CXCR2 Xu, Baolin Janicova, Andrea Vollrath, Jan Tilmann Störmann, Philipp Martin, Lukas Marzi, Ingo Wutzler, Sebastian Hildebrand, Frank Ehnert, Sabrina Relja, Borna Mol Med Research Article BACKGROUND: Club Cell protein (CC)16 correlates with lung injury and respiratory complications, which are in part triggered by polymorphonuclear leukocytes (PMNL) in severely traumatized patients (TP). CC16 exerts anti-inflammatory and immunosuppressive effects, however, its influence on PMNL functions after trauma is unknown. Here, we evaluated whether CC16 present in sera from TP could modify the biological functions of PMNL. METHODS: Sera from 16 severely injured TP without pneumonia (no P, n = 8) or with pneumonia (P, n = 8) were collected at admission to emergency department (ED) and 1 day prior pneumonia and pre-incubated with or without anti-CC16 antibody for CC16 neutralization. Samples from the equal post-injury days in the corresponding no P group were used. Neutrophils were isolated from healthy volunteers (HV, n = 5) and incubated with 20% of the serum medium from TP, respectively. In PMNL, CD62L, CD11b/CD18 and CD31 expression, migratory capacity, phagocytosis rate, oxidative burst and apoptosis were investigated. In isolated PMNL, CXCR1 and CXCR2 were neutralized before stimulation with CC16, and oxidative burst, phagocytosis and apoptosis were analyzed in neutrophils and their subsets. RESULTS: Serum from the P group enhanced significantly PMNL migration compared to no P group, while CC16-neutralization further increased the migratory rate of PMNL in both groups. CC16-neutralization increased significantly the expression of CD62L in the P group at ED. Oxidative burst was significantly increased in the P group vs. no P during the study period. CC16 seemed to have no influence on oxidative burst and phagocytosis in TP. However, in a more controlled study design, CC16 induced a significant increase of oxidative burst and a decrease of apoptosis of CD16(+) granulocytes. These effects were markedly observed in mature CD16(bright)CD62L(bright) and immune suppressive CD16(bright)CD62L(dim) neutrophils. In mature subset, CXCR1 and CXCR2 neutralization diminished CC16-induced effects. CONCLUSIONS: CC16 in sera from multiply traumatized patients, notably of those with pneumonia, has significant effects on PMNL. The results suggest an association of CC16 with CXCR1 and CXCR2. Our data suggest that CC16 reduces the migratory capacity of PMNL and thus modulates their function in patients with respiratory complications after trauma. BioMed Central 2019-10-30 /pmc/articles/PMC6822417/ /pubmed/31666007 http://dx.doi.org/10.1186/s10020-019-0115-0 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Xu, Baolin Janicova, Andrea Vollrath, Jan Tilmann Störmann, Philipp Martin, Lukas Marzi, Ingo Wutzler, Sebastian Hildebrand, Frank Ehnert, Sabrina Relja, Borna Club cell protein 16 in sera from trauma patients modulates neutrophil migration and functionality via CXCR1 and CXCR2 |
title | Club cell protein 16 in sera from trauma patients modulates neutrophil migration and functionality via CXCR1 and CXCR2 |
title_full | Club cell protein 16 in sera from trauma patients modulates neutrophil migration and functionality via CXCR1 and CXCR2 |
title_fullStr | Club cell protein 16 in sera from trauma patients modulates neutrophil migration and functionality via CXCR1 and CXCR2 |
title_full_unstemmed | Club cell protein 16 in sera from trauma patients modulates neutrophil migration and functionality via CXCR1 and CXCR2 |
title_short | Club cell protein 16 in sera from trauma patients modulates neutrophil migration and functionality via CXCR1 and CXCR2 |
title_sort | club cell protein 16 in sera from trauma patients modulates neutrophil migration and functionality via cxcr1 and cxcr2 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822417/ https://www.ncbi.nlm.nih.gov/pubmed/31666007 http://dx.doi.org/10.1186/s10020-019-0115-0 |
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