PNNL

Abstract

Polymorphonuclear neutrophils play an important role in mediating the innate immune response after severe traumatic injury; however, the cellular proteome response to traumatic condition is still largely unknown. Here we report the first comprehensive comparative proteome profiling study of human neutrophils from severe trauma patients and healthy controls. A total of 254 proteins were observed with significant abundance change following injury. An integrated analysis of proteomic data and genomic data revealed that for the majority of proteins, the protein abundance change and mRNA abundances change were consistent. Moreover, increased protein secretion was inferred as one of the mechanisms contributing to the observed discrepancy between protein and mRNA abundance changes. Functional analyses of the altered proteins showed that many of these proteins were involved in known immune response pathways, protein biosynthesis, protein transport, NRF2-mediated oxidative stress response, the ubiquitin-proteasome system, and apoptosis, suggesting increased neutrophil activation and inhibited neutrophil apoptosis in response to trauma. While the general observation of neutrophil response to trauma was in good agreement with prior knowledge, the functions of most of the altered proteins were not known for neutrophils or inflammatory diseases. Therefore, the study not only reveals an overall picture of functional neutrophil response to trauma at the proteome level, but also provides a rich resource of trauma-associated neutrophil proteins that will be valuable for further studies of the functions of individual proteins in neutrophils in relevant diseases.