C-Terminal Alpha-1 Antitrypsin Peptide: A New Sepsis Biomarker with Immunomodulatory Function
Systemic inflammatory response syndrome (SIRS) is a life threatening condition and the leading cause of death in intensive care units. Although single aspects of pathophysiology have been described in detail, numerous unknown mediators contribute to the progression of this complex disease. The aim o...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2016/6129437 |
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| author | Nancy Blaurock Diana Schmerler Kerstin Hünniger Oliver Kurzai Katrin Ludewig Michael Baier Frank Martin Brunkhorst Diana Imhof Michael Kiehntopf |
| author_facet | Nancy Blaurock Diana Schmerler Kerstin Hünniger Oliver Kurzai Katrin Ludewig Michael Baier Frank Martin Brunkhorst Diana Imhof Michael Kiehntopf |
| author_sort | Nancy Blaurock |
| collection | DOAJ |
| description | Systemic inflammatory response syndrome (SIRS) is a life threatening condition and the leading cause of death in intensive care units. Although single aspects of pathophysiology have been described in detail, numerous unknown mediators contribute to the progression of this complex disease. The aim of this study was to elucidate the pathophysiological role of CAAP48, a C-terminal alpha-1 antitrypsin fragment, that we found to be elevated in septic patients and to apply this peptide as diagnostic marker for infectious and noninfectious etiologies of SIRS. Incubation of human polymorphonuclear neutrophils with synthetic CAAP48, the SNP-variant CAAP47, and several control peptides revealed intense neutrophil activation, induction of neutrophil chemotaxis, reduction of neutrophil viability, and release of cytokines. We determined the abundance of CAAP48 in patients with severe sepsis, severe SIRS of noninfectious origin, and viral infection. CAAP48 levels were 3-4-fold higher in patients with sepsis compared to SIRS of noninfectious origin and allowed discrimination of those patients with high sensitivity and specificity. Our results suggest that CAAP48 is a promising discriminatory sepsis biomarker with immunomodulatory functions, particularly on human neutrophils, supporting its important role in the host response and pathophysiology of sepsis. |
| format | Article |
| id | doaj-art-623b3c71f26d48fbac5d971ecacb2dda |
| institution | OA Journals |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-623b3c71f26d48fbac5d971ecacb2dda2025-08-20T02:24:00ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/61294376129437C-Terminal Alpha-1 Antitrypsin Peptide: A New Sepsis Biomarker with Immunomodulatory FunctionNancy Blaurock0Diana Schmerler1Kerstin Hünniger2Oliver Kurzai3Katrin Ludewig4Michael Baier5Frank Martin Brunkhorst6Diana Imhof7Michael Kiehntopf8Department of Clinical Chemistry and Laboratory Medicine, Jena University Hospital, Erlanger Allee 101, 07747 Jena, GermanyDepartment of Clinical Chemistry and Laboratory Medicine, Jena University Hospital, Erlanger Allee 101, 07747 Jena, GermanySeptomics Research Center, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute (HKI), Albert-Einstein-Street 10, 07745 Jena, GermanySeptomics Research Center, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute (HKI), Albert-Einstein-Street 10, 07745 Jena, GermanyCenter for Sepsis Control and Care (CSCC), Jena University Hospital, Erlanger Allee 101, 07747 Jena, GermanyDepartment for Medical Microbiology, Jena University Hospital, Erlanger Allee 101, 07747 Jena, GermanyCenter for Sepsis Control and Care (CSCC), Jena University Hospital, Erlanger Allee 101, 07747 Jena, GermanyPharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, Brühler Street 7, 53119 Bonn, GermanyDepartment of Clinical Chemistry and Laboratory Medicine, Jena University Hospital, Erlanger Allee 101, 07747 Jena, GermanySystemic inflammatory response syndrome (SIRS) is a life threatening condition and the leading cause of death in intensive care units. Although single aspects of pathophysiology have been described in detail, numerous unknown mediators contribute to the progression of this complex disease. The aim of this study was to elucidate the pathophysiological role of CAAP48, a C-terminal alpha-1 antitrypsin fragment, that we found to be elevated in septic patients and to apply this peptide as diagnostic marker for infectious and noninfectious etiologies of SIRS. Incubation of human polymorphonuclear neutrophils with synthetic CAAP48, the SNP-variant CAAP47, and several control peptides revealed intense neutrophil activation, induction of neutrophil chemotaxis, reduction of neutrophil viability, and release of cytokines. We determined the abundance of CAAP48 in patients with severe sepsis, severe SIRS of noninfectious origin, and viral infection. CAAP48 levels were 3-4-fold higher in patients with sepsis compared to SIRS of noninfectious origin and allowed discrimination of those patients with high sensitivity and specificity. Our results suggest that CAAP48 is a promising discriminatory sepsis biomarker with immunomodulatory functions, particularly on human neutrophils, supporting its important role in the host response and pathophysiology of sepsis.http://dx.doi.org/10.1155/2016/6129437 |
| spellingShingle | Nancy Blaurock Diana Schmerler Kerstin Hünniger Oliver Kurzai Katrin Ludewig Michael Baier Frank Martin Brunkhorst Diana Imhof Michael Kiehntopf C-Terminal Alpha-1 Antitrypsin Peptide: A New Sepsis Biomarker with Immunomodulatory Function Mediators of Inflammation |
| title | C-Terminal Alpha-1 Antitrypsin Peptide: A New Sepsis Biomarker with Immunomodulatory Function |
| title_full | C-Terminal Alpha-1 Antitrypsin Peptide: A New Sepsis Biomarker with Immunomodulatory Function |
| title_fullStr | C-Terminal Alpha-1 Antitrypsin Peptide: A New Sepsis Biomarker with Immunomodulatory Function |
| title_full_unstemmed | C-Terminal Alpha-1 Antitrypsin Peptide: A New Sepsis Biomarker with Immunomodulatory Function |
| title_short | C-Terminal Alpha-1 Antitrypsin Peptide: A New Sepsis Biomarker with Immunomodulatory Function |
| title_sort | c terminal alpha 1 antitrypsin peptide a new sepsis biomarker with immunomodulatory function |
| url | http://dx.doi.org/10.1155/2016/6129437 |
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