The Dynamics of Circulating Heparin-Binding Protein : Implications for Its Use as a Biomarker
(2022) In Journal of Innate Immunity 14(5). p.447-460- Abstract
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... (More)
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.
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- author
- Fisher, Jane LU ; Kahn, Fredrik LU ; Wiebe, Elena ; Gustafsson, Pontus ; Kander, Thomas LU ; Mellhammar, Lisa LU ; Bentzer, Peter LU and Linder, Adam LU
- organization
-
- Translational Sepsis research (research group)
- Neutrophils – new mechanisms and new biomarkers (research group)
- Lund University Bioimaging Center
- Clinical Research in Anaesthesia and Intensive Care Medicine (research group)
- Fluid resuscitation in critical illness (research group)
- SEBRA Sepsis and Bacterial Resistance Alliance (research group)
- publishing date
- 2022
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Innate Immunity
- volume
- 14
- issue
- 5
- pages
- 447 - 460
- publisher
- Karger
- external identifiers
-
- scopus:85122310351
- pmid:34965528
- ISSN
- 1662-811X
- DOI
- 10.1159/000521064
- language
- English
- LU publication?
- yes
- additional info
- © 2021 The Author(s). Published by S. Karger AG, Basel.
- id
- e31d714e-424a-40e5-879c-7c469b2a004b
- date added to LUP
- 2022-01-03 10:45:13
- date last changed
- 2024-09-10 06:20:35
@article{e31d714e-424a-40e5-879c-7c469b2a004b, abstract = {{<p>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.</p>}}, author = {{Fisher, Jane and Kahn, Fredrik and Wiebe, Elena and Gustafsson, Pontus and Kander, Thomas and Mellhammar, Lisa and Bentzer, Peter and Linder, Adam}}, issn = {{1662-811X}}, language = {{eng}}, number = {{5}}, pages = {{447--460}}, publisher = {{Karger}}, series = {{Journal of Innate Immunity}}, title = {{The Dynamics of Circulating Heparin-Binding Protein : Implications for Its Use as a Biomarker}}, url = {{http://dx.doi.org/10.1159/000521064}}, doi = {{10.1159/000521064}}, volume = {{14}}, year = {{2022}}, }