Potential biomarkers of an exaggerated response to endotoxemia.
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.
Kasthuri
R S
RS
Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Wroblewski
M
M
Jilma
B
B
Key
N S
NS
Nelsestuen
G L
GL
D000209:Acute-Phase Proteins / Q000032:analysis / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D053305:Apolipoprotein C-III / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D015415:Biomarkers / Q000097:blood* / Q000378:metabolism; D001798:Blood Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D001831:Body Temperature / Q000187:drug effects; D002097:C-Reactive Protein / Q000032:analysis / Q000378:metabolism; D003167:Complement Activation / Q000187:drug effects; D050718:Complement C1 Inhibitor Protein / Q000032:analysis / Q000378:metabolism; D019446:Endotoxemia / Q000097:blood* / Q000139:chemically induced; D004731:Endotoxins / Q000494:pharmacology; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D008297:Male; D020543:Proteome / Q000032:analysis / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000032:analysis / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000209:Acute-Phase Proteins; D053305:Apolipoprotein C-III; D015415:Biomarkers; D001798:Blood Proteins; D050718:Complement C1 Inhibitor Protein; D004731:Endotoxins; D020543:Proteome; D000685:Serum Amyloid A Protein; D002097:C-Reactive Protein