DAMPs and NETs in Sepsis
- 1Center for Immunology and Inflammation, Feinstein Institute for Medical Research, United States
- 2Elmezzi Graduate School of Molecular Medicine, United States
- 3Donald and Barbara Zucker School of Medicine at Hofstra-Northwell, United States
- 4Department of Surgery, Donald and Barbara Zucker School of Medicine at Hofstra-Northwell, United States
- 5Department of Surgery and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra-Northwell, United States
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 understating of DAMPs, NETs and their interaction is crucial for the understanding of the pathophysiology of sepsis and for the development of novel sepsis therapeutics.
Keywords: DAMPs (damage-associated molecular patterns), NETs (neutrophil extracellular traps, Sepsis, HMGB1 (high-mobility group box 1), CIRP, histone, Neutrophils (PMNs)
Received: 14 May 2019;
Accepted: 11 Oct 2019.
Copyright: © 2019 Denning, Aziz, Gurien and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Dr. Monowar Aziz, Feinstein Institute for Medical Research, Center for Immunology and Inflammation, Manhasset, 11030, New York, United States, firstname.lastname@example.org
Prof. Ping Wang, Feinstein Institute for Medical Research, Center for Immunology and Inflammation, Manhasset, 11030, New York, United States, PWang@northwell.edu