The dynamics of circulating heparin-binding protein (HBP) - implications for its use as a biomarker

Abstract

Background Heparin Binding Protein (HBP) is a promising new biomarker for the development and severity of sepsis. To guide the use of HBP as a biomarker it is important to understand the factors that may lead to false positive or negative results. The mechanisms that could lead to falsely elevated HBP levels include inappropriate release and inadequate clearance of HBP by the responsible cells and organs. HBP is presumably released only by neutrophils and the organs responsible for its elimination are unknown. Therefore, in this study we aimed to determine whether non-neutrophil cells can be a source of HBP in the circulation and which organs are responsible for its removal.Results We measured HBP in two cohorts of neutropenic patients and found that 12% and 19% of patients in each cohort respectively had detectable HBP levels. In vitro, we found that three leukemia-derived monocytic cell lines and healthy CD14 + monocytes constitutively released detectable levels of HBP. Next we injected HBP intravenously in rats found that plasma levels of HBP decreased rapidly, with a distribution half-life below 10 minutes and an elimination half-life of 1–2 hours. 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.Conclusions HBP can be found in some neutropenic patients. Other than neutrophils, malignant myeloid cells and monocytic cells may be an additional source of HBP. HBP disappears rapidly from the circulation and distributes primarily to liver hepatocytes and spleen monocytes/macrophages. The impact of hematologic malignancies and liver diseases on plasma HBP levels should be explored further in clinical studies.