The Modulation of Septic Shock: A Proteomic Approach

Abstract

Sepsis poses a significant challenge due its lethality, involving multiple organ dysfunction and impaired immune responses. Among several factors affecting sepsis, monocytes play a crucial role; however, their phenotype, proteomic profile, and function in septic shock remain unclear. Our aim was to fully characterize the subpopulations and proteomic profiles of monocytes seen in septic shock cases and discuss their possible impact on the disease. Peripheral blood monocyte subpopulations were phenotype based on CD14/CD16 expression by flow cytometry, and proteins were extracted from the monocytes of individuals with septic shock and healthy controls to identify changes in the global protein expression in these cells. Analysis using 2D-nanoUPLC-UDMSE identified 67 differentially expressed proteins in shock patients compared to controls, in which 44 were upregulated and 23 downregulated. These proteins are involved in monocyte reprogramming, immune dysfunction, severe hypotension, hypo-responsiveness to vasoconstrictors, vasodilation, endothelial dysfunction, vascular injury, and blood clotting, elucidating the disease severity and therapeutic challenges of septic shock. This study identified critical biological targets in monocytes that could serve as potential biomarkers for the diagnosis, prognosis, and treatment of septic shock, providing new insights into the pathophysiology of the disease.

Keywords: blood clotting; hypotension; monocytes; secreted proteins; systemic dysfunction; vascular injury.

Figure 1

The biological components and interactions of differentially expressed proteins. The major cellular components involved are downregulated (A) and upregulated (B). The main biological processes participating in differentially expressed proteins are (C) down- and (D) upregulated. The interactions between differentially expressed proteins are not direct. However, they influence several molecules that communicate directly. Blue represents downregulated genes, red indicates upregulated genes, and green indicates the interaction genes of the FunRich database (E).