Protein biomarkers in the peripheral blood could potentially be used as early indicators of sepsis and a means to stratify patients for clinical trials. Although individual molecular markers have been proposed for sepsis, none has clinical utility. The global changes in plasma proteins over the clinical course of sepsis have not been characterized using proteomic methods. We used cecal ligation and puncture to induce polymicrobial sepsis in mice and generated plasma protein profiles using 2-D DIGE of plasma from septic mice and surgical controls. Replicate cohorts (n = 3) of 4-7 animals each were used to identify 62 gel features that changed significantly (Student's t-test, p<0.05). We identified a suite of plasma proteins that describe uniquely the host plasma response to polymicrobial septic insult. Principal components analysis of protein abundance showed that ∼90% of the variability between samples was due to sepsis. In addition to canonical acute phase proteins, we identified proteins that are associated with metabolic changes (e.g. α-2 HS glycoprotein and zinc α-2 glycoprotein) consistent with the pathophysiology of sepsis. The panel of sepsis-associated molecular markers identified herein may prove useful in the diagnosis and categorization of sepsis.
- Cecal ligation and puncture
- Differential in-gel electrophoresis
- Principal components analysis