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.

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.

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Eine typische Reaktion bei der Beurteilung von Unternehmensskandalen ist die Vermutung, dass wenige unmoralisch 1 denkende und handelnde Manager, sogenannte "bad apples" für unethisches oder kriminelles Handeln von Unternehmen verantwortlich sind. 2 Dahinter steht die Annahme von bewusstem und rationalem Handeln der Entscheider. Folgt man dieser Annahme, so können unmoralische Handlungen nur von Menschen mit unmoralischer Intention vollzogen werden. Folgerichtig setzen auch die Methoden wie Complianceund Interne Kontrollsysteme (IKS) sowie Verhaltenskodizes, die in Unternehmen zur Sicherstellung des legalen und ethischen Handelns der Mitarbeiter und Entscheider implementiert werden, ein bewusstes, informiertes und rationales Handeln dieser Personen voraus. Dies spiegelt sich in den an Business Schools und Hochschulen gelehrten deskriptiven ethischen Entscheidungsmodellen wie dem kanonischen Modell von Rest (1986) wider, das weiter unten näher beschrieben wird. Hier setzen aber auch normative Ethiken an, die unternehmerisches Handeln im Einklang mit einem (religiösen) Wertesystem fordern. Die Frage stellt sich, ob das unterstellte Paradigma ethischen Entscheidens und Handelns im Unternehmen zutreffend ist. Im vorliegenden Beitrag wird eine ethische beziehungsweise unethische Entscheidung der pragmatischen Definition von Jones folgend verstanden als "a decision that is both legal or morally acceptable to the larger community. Conversely, an unethical decision is either illegal or morally unacceptable to the larger community." 3 Zweifel an der Gültigkeit der "bad apples"-Vermutung kommen immer dann auf, wenn das Handeln nicht zu den glaubwürdig vorgetragenen Überzeugungen des unethisch Handelnden passt. So reagieren angesehene Vertreter der Textilindustrie auf Vorwürfe bezüglich der Umwelt-und Sozialstandards der Produktionsbedingungen in Asien mit den folgenden stereotypischen Argumenten, die sich so oder ähnlich in Interviews und Unternehmensstellungnahmen finden: 1) die Vertragspartner sind Zwischenhändler, die ihrerseits für die Organisation ordnungsgemäßer Produktionsbedingungen verantwortlich 1 Die Begriffe moralisch und ethisch werden in dem vorliegenden Beitrag synonym verwendet. 2 DAVID DE CREMER/ ANN. E. TENBRUNSEL (Hg), Behavioral Business Ethics. Shaping an Emerging Field, New York 2012. 3 THOMAS M. JONES, Ethical decision making by individuals in organizations. An issue contingent model. In: Academy of Management Review 16 (1991) 366-395, hier 367. 4 Entsprechende Zitate finden sich zum Beispiel in dem Dokumentarfilm von CHRISTIAN JENTZSCH und MICHAEL HÖFT "Der Preis der Blue-Jeans", Deutschland 2012.