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The Dynamics of Circulating Heparin-Binding Protein: Implications for Its Use as a Biomarker
Heparin-binding protein (HBP) is a promising biomarker for the development and severity of sepsis. To guide its use, it is important to understand the factors that could lead to false-positive or negative results, such as inappropriate release and inadequate clearance of HBP. HBP is presumably relea...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
S. Karger AG
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9485916/ https://www.ncbi.nlm.nih.gov/pubmed/34965528 http://dx.doi.org/10.1159/000521064 |
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author | Fisher, Jane Kahn, Fredrik Wiebe, Elena Gustafsson, Pontus Kander, Thomas Mellhammar, Lisa Bentzer, Peter Linder, Adam |
author_facet | Fisher, Jane Kahn, Fredrik Wiebe, Elena Gustafsson, Pontus Kander, Thomas Mellhammar, Lisa Bentzer, Peter Linder, Adam |
author_sort | Fisher, Jane |
collection | PubMed |
description | Heparin-binding protein (HBP) is a promising biomarker for the development and severity of sepsis. To guide its use, it is important to understand the factors that could lead to false-positive or negative results, such as inappropriate release and inadequate clearance of HBP. HBP is presumably released only by neutrophils, and the organs responsible for its elimination are unknown. In this study, we aimed to determine whether non-neutrophil cells can be a source of circulating HBP and which organs are responsible for its removal. We found that in two cohorts of neutropenic patients, 12% and 19% of patients in each cohort, respectively, had detectable plasma HBP levels. In vitro, three leukemia-derived monocytic cell lines and healthy CD14+ monocytes constitutively released detectable levels of HBP. When HBP was injected intravenously in rats, we found that plasma levels of HBP decreased rapidly, with a distribution half-life below 10 min and an elimination half-life of 1–2 h. We measured HBP levels in the liver, spleen, kidneys, lungs, and urine using both ELISA and immunofluorescence quantitation, and found that the majority of HBP was present in the liver, and a small amount was present in the spleen. Immunofluorescence imaging indicated that HBP is associated mainly with hepatocytes in the liver and monocytes/macrophages in the spleen. The impact of hematologic malignancies and liver diseases on plasma HBP levels should be explored further in clinical studies. |
format | Online Article Text |
id | pubmed-9485916 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | S. Karger AG |
record_format | MEDLINE/PubMed |
spelling | pubmed-94859162022-09-23 The Dynamics of Circulating Heparin-Binding Protein: Implications for Its Use as a Biomarker Fisher, Jane Kahn, Fredrik Wiebe, Elena Gustafsson, Pontus Kander, Thomas Mellhammar, Lisa Bentzer, Peter Linder, Adam J Innate Immun Research Article Heparin-binding protein (HBP) is a promising biomarker for the development and severity of sepsis. To guide its use, it is important to understand the factors that could lead to false-positive or negative results, such as inappropriate release and inadequate clearance of HBP. HBP is presumably released only by neutrophils, and the organs responsible for its elimination are unknown. In this study, we aimed to determine whether non-neutrophil cells can be a source of circulating HBP and which organs are responsible for its removal. We found that in two cohorts of neutropenic patients, 12% and 19% of patients in each cohort, respectively, had detectable plasma HBP levels. In vitro, three leukemia-derived monocytic cell lines and healthy CD14+ monocytes constitutively released detectable levels of HBP. When HBP was injected intravenously in rats, we found that plasma levels of HBP decreased rapidly, with a distribution half-life below 10 min and an elimination half-life of 1–2 h. We measured HBP levels in the liver, spleen, kidneys, lungs, and urine using both ELISA and immunofluorescence quantitation, and found that the majority of HBP was present in the liver, and a small amount was present in the spleen. Immunofluorescence imaging indicated that HBP is associated mainly with hepatocytes in the liver and monocytes/macrophages in the spleen. The impact of hematologic malignancies and liver diseases on plasma HBP levels should be explored further in clinical studies. S. Karger AG 2021-12-29 /pmc/articles/PMC9485916/ /pubmed/34965528 http://dx.doi.org/10.1159/000521064 Text en Copyright © 2021 by The Author(s). Published by S. Karger AG, Basel https://creativecommons.org/licenses/by-nc/4.0/This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. |
spellingShingle | Research Article Fisher, Jane Kahn, Fredrik Wiebe, Elena Gustafsson, Pontus Kander, Thomas Mellhammar, Lisa Bentzer, Peter Linder, Adam The Dynamics of Circulating Heparin-Binding Protein: Implications for Its Use as a Biomarker |
title | The Dynamics of Circulating Heparin-Binding Protein: Implications for Its Use as a Biomarker |
title_full | The Dynamics of Circulating Heparin-Binding Protein: Implications for Its Use as a Biomarker |
title_fullStr | The Dynamics of Circulating Heparin-Binding Protein: Implications for Its Use as a Biomarker |
title_full_unstemmed | The Dynamics of Circulating Heparin-Binding Protein: Implications for Its Use as a Biomarker |
title_short | The Dynamics of Circulating Heparin-Binding Protein: Implications for Its Use as a Biomarker |
title_sort | dynamics of circulating heparin-binding protein: implications for its use as a biomarker |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9485916/ https://www.ncbi.nlm.nih.gov/pubmed/34965528 http://dx.doi.org/10.1159/000521064 |
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