Abstract
Bacterial endotoxin (lipopolysaccharide, LPS) is the major component of the outer leaflet of the outer membrane in Gram-negative bacteria. During severe infections, bacteria may reach the blood circuit of humans, and endotoxins may be released from the bacteria due to cell division or cell death. In particular enterobacterial forms of LPS represent extremely strong activator molecules of the human immune system causing a rapid induction of cytokine production in monocytes and macrophages. Various mammalian blood proteins have been documented to display LPS binding activities mediating normally decreasing effects in the biological activity of LPS. In more recent studies, the essential systemic oxygen transportation protein hemoglobin (Hb) has been shown to amplify LPS-induced cytokine production on immune cells. The mechanism responsible for this effect is poorly understood. Here, we characterize the interaction of hemoglobin with LPS by using biophysical methods. The data presented, revealing the changes of the type and size of supramolecular aggregates of LPS in the presence of Hb, allow a better understanding of the hemoglobin-induced increase in bioactivity of LPS.
Keywords: Lipopolysaccharide, Fourier-Transform Infrared Spectroscopy (FTIR), Isothermal Titration Calorimetry (ITC), human mononuclear cells (MNC), Backscattering Analyses
Medicinal Chemistry
Title: Biophysical Characterization of the Interaction of Endotoxins with Hemoglobins
Volume: 3 Issue: 1
Author(s): Jorg Howe, Malte Hammer, Christian Alexander, Manfred Rossle, Karin Fournier, Jean-Pierre Mach, Thierry Waelli, Reginald M. Gorczynski, Artur J. Ulmer, Ulrich Zahringer and Klaus Brandenburg
Affiliation:
Keywords: Lipopolysaccharide, Fourier-Transform Infrared Spectroscopy (FTIR), Isothermal Titration Calorimetry (ITC), human mononuclear cells (MNC), Backscattering Analyses
Abstract: Bacterial endotoxin (lipopolysaccharide, LPS) is the major component of the outer leaflet of the outer membrane in Gram-negative bacteria. During severe infections, bacteria may reach the blood circuit of humans, and endotoxins may be released from the bacteria due to cell division or cell death. In particular enterobacterial forms of LPS represent extremely strong activator molecules of the human immune system causing a rapid induction of cytokine production in monocytes and macrophages. Various mammalian blood proteins have been documented to display LPS binding activities mediating normally decreasing effects in the biological activity of LPS. In more recent studies, the essential systemic oxygen transportation protein hemoglobin (Hb) has been shown to amplify LPS-induced cytokine production on immune cells. The mechanism responsible for this effect is poorly understood. Here, we characterize the interaction of hemoglobin with LPS by using biophysical methods. The data presented, revealing the changes of the type and size of supramolecular aggregates of LPS in the presence of Hb, allow a better understanding of the hemoglobin-induced increase in bioactivity of LPS.
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Cite this article as:
Howe Jorg, Hammer Malte, Alexander Christian, Rossle Manfred, Fournier Karin, Mach Jean-Pierre, Waelli Thierry, Gorczynski M. Reginald, Ulmer J. Artur, Zahringer Ulrich and Brandenburg Klaus, Biophysical Characterization of the Interaction of Endotoxins with Hemoglobins, Medicinal Chemistry 2007; 3 (1) . https://dx.doi.org/10.2174/157340607779317625
DOI https://dx.doi.org/10.2174/157340607779317625 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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