Microparticles as novel biomarkers/effectors in severe sepsis

Abstract

Microparticles (MP) are submicron structures produced by all cells upon activation or apoptosis that act as a non-soluble means of communication between cells. They ferry proteins, bioactive lipids, RNA and receptors, as well as ridding cells of redundant organelles and toxins. They have been recently investigated for their pathophysiological role and as potential biomarkers/effectors in many diseases. In severe sepsis, studies of MP so far have produced inconsistent and even conflicting results. In this project, it was demonstrated that cell derived MP subsets vary according to the cause of severe sepsis (community acquired pneumonia (CAP) or faecal peritonitis (FP)), where CAP patients had higher levels of circulating MP. Surprisingly, FP patients MP levels were comparable to healthy volunteers. Further stratification of MP subsets according to their expression of the protein alpha-2-macroglobulin (A2M) has yielded better differentiation between the two diseases. The A2M expressing MP were significantly higher in survivors of community acquired pneumonia sepsis, but there was no similar association in patient with FP. Granulocyte macrophage colony-stimulating factor (GM-CSF) and interferon γ (IFN- γ) are being studied as possible adjuvant therapies in sepsis. They seem to reverse the immune-paresis that ensues after the initial insult. MP produced from whole blood stimulated with GM-CSF and IFN- γ were studied in this project. Both GM-CSF and IFN- γ increased MP expressing A2M over control. These MP elicited a pro-inflammatory phenotype when incubated with neutrophils or endothelial cells which may contribute to the potential benefits of GM-CSF and IFN- γ in severe sepsis.