The Dynamics of Circulating Heparin-Binding Protein: Implications for Its Use as a Biomarker.

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 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.

• Authors: Jane Fisher, Fredrik Kahn, Elena Wiebe, Pontus Gustafsson, Thomas Kander, Lisa Mellhammar, Peter Bentzer, Adam Linder
• Journal: Journal of innate immunity (J Innate Immun) Vol. 14 Issue 5 Pg. 447-460 ( 2022) ISSN: 1662-8128 [Electronic] Switzerland
• PMID: 34965528 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Author(s). Published by S. Karger AG, Basel.

Chemical References

• AZU1 protein, human
• Antimicrobial Cationic Peptides
• Biomarkers
• Blood Proteins

Topics

• Animals
• Antimicrobial Cationic Peptides (metabolism)
• Biomarkers
• Blood Proteins (metabolism)
• Humans
• Rats
• Sepsis