DAMPs and NETs in Sepsis

Abstract

Sepsis is a deadly inflammatory syndrome caused by an exaggerated immune response to infection. Much has been focused on host response to pathogens mediated through the interaction of pathogen-associated molecular patterns (PAMPs) and pattern recognition receptors (PRRs). PRRs are also activated by host nuclear, mitochondrial, and cytosolic proteins, known as damage-associated molecular patterns (DAMPs) that are released from cells during sepsis. Some well described members of the DAMP family are extracellular cold-inducible RNA-binding protein (eCIRP), high mobility group box 1 (HMGB1), histones, and adenosine triphosphate (ATP). DAMPs are released from the cell through inflammasome activation or passively following cell death. Similarly, neutrophil extracellular traps (NETs) are released from neutrophils during inflammation. NETs are webs of extracellular DNA decorated with histones, myeloperoxidase, and elastase. Although NETs contribute to pathogen clearance, excessive NET formation promotes inflammation and tissue damage in sepsis. Here, we review DAMPs and NETs and their crosstalk in sepsis with respect to their sources, activation, release, and function. A clear grasp of DAMPs, NETs and their interaction is crucial for the understanding of the pathophysiology of sepsis and for the development of novel sepsis therapeutics.

Defining Community-Acquired Pneumonia as a Public Health Threat: Arguments in Favor from Spanish Investigators

“…Between 10% and 30% of patients with bacteremic pneumococcal CAP present cardiovascular events, the most affected being those with preexisting cardiovascular disease [38][39][40]. A possible explanation for this cardiac tissue damage is that the substances produced, including Damage-Associated Molecular Patterns (DAMPs), may maintain inflammation during severe lung tissue cell injury, thus affecting other host cells and aggravating heart cell injury [41].…”

Extracellular CIRP induces macrophage endotoxin tolerance through IL-6R–mediated STAT3 activation

“…In macrophages, eCIRP induces inflammation by binding to its receptor, TLR4 (26). However, akin to other DAMPs (29,30), eCIRP may have numerous receptors other than TLR4 to stimulate immune responses. eCIRP-mediated inflammation through TLR4 has been well studied, while its role in promoting macrophages' immune tolerance has not been explored.…”

From sepsis to acute respiratory distress syndrome (ARDS): emerging preventive strategies based on molecular and genetic researches

“…This conclusion further shows that the detection of related gene expression and variants has an important role in the prediction and prevention of the occurrence and development of ARDS. In critically ill patients, distant injury leading to subsequent lung failure is associated with DAMPs released by apoptotic cells [64], which are detected in plasma and enable clinicians to preliminarily diagnose ARDS in advance. In this review, we summarize the emerging plasma biomarkers for predicting and serving as targets to regulate sepsis-related ARDS.…”