Potential biomarkers of an exaggerated response to endotoxemia |
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Authors: | R. S. Kasthuri M. Wroblewski B. Jilma N. S. Key G. L. Nelsestuen |
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Affiliation: | a Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, Minnesota, USAb Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota, USAc Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austriad Department of Pharmaceutics, University of Florida, Gainesville, Florida, USAe Division of Hematology and Oncology, University of North Carolina, Chapel Hill, North Carolina, USA |
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Abstract: | Serial plasma protein analysis was used to study the acute plasma proteome response to endotoxemia (presence of toxic bacterial products called endotoxins in the blood stream). Plasma samples from healthy volunteers before and multiple time points up to 24 h following administration of low-dose endotoxin were evaluated. Plasma protein profiles were obtained by rapid extraction of whole plasma followed by analysis with matrix-assisted laser desorption ionisation-time of flight mass spectrometry. The profiles were unique to each individual and stable over the time of the experiment. Administration of low-dose endotoxin caused profound change in six of 18 individuals. At 8 h many proteins showed quantitative oxidation, in addition to the appearance of new components and disappearance of common baseline components. An exceptionally intense new component at 4154 mass units was identified as the activation peptide of C1 esterase inhibitor. While recovery of baseline protein structure was nearly complete by 24 h, serum amyloid A, an acute-phase reactant, was still increasing and minor profile changes persisted. Clinical features did not distinguish these extreme responders from others, suggesting that plasma proteome changes offered unique insights into and potential biomarkers of subclinical events following endotoxin exposure. |
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Keywords: | Biomarkers acute-phase reactants complement human lipopolysaccharide |
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