Abstract
Early events triggered by posttrauma/hemorrhagic shock currently represent a leading cause of morbidity and mortality in these patients. The causative agents of these events have been associated with increased neutrophil priming secondary to shock-dependent alterations of mesenteric lymph. Previous studies have suggested that unknown soluble components of the postshock mesenteric lymph are main drivers of these events. In the present study, we applied a label-free proteomics approach to further delve into the early proteome changes of the mesenteric lymph in response to hemorrhagic shock. Time-course analyses were performed by sampling the lymph every 30 min after shock up until 3 h (the time window within which a climax in neutrophil priming was observed). There are novel, transient early post-hemorrhagic shock alterations to the proteome and previously undocumented postshock protein alterations. These results underlie the triggering of coagulation and proinflammatory responses secondary to trauma/hemorrhagic shock, metabolic deregulation and apoptosis, and alterations to proteases/antiproteases homeostasis, which are suggestive of the potential implication of extracellular matrix proteases in priming neutrophil activation. Finally, there is a likely correlation between early postshock mesenteric lymph-mediated neutrophil priming and proteomics changes, above all protease/antiproteases impaired homeostasis (especially of serine proteases and metalloproteases).