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Review
. 2018 Feb 1;197(3):300-309.
doi: 10.1164/rccm.201612-2460PP.

The Role of Danger Signals in the Pathogenesis and Perpetuation of Critical Illness

Kevin C Ma  1   2 , Edward J Schenck  1   2 , Maria A Pabon  3   2 , Augustine M K Choi  1   2
Affiliations
Review

The Role of Danger Signals in the Pathogenesis and Perpetuation of Critical Illness

Kevin C Ma et al. Am J Respir Crit Care Med. .
No abstract available

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Figures

Figure 1.
Figure 1.
Proposed schema for the pathogenesis of damage-associated molecular pattern (DAMP)- and pathogen-associated molecular pattern (PAMP)-mediated local and distal organ injury during critical illness. (1) Infection or sterile organ injury, such as trauma, burns, or pancreatitis, leads to direct initial insult. (2) Infection and local tissue injury releases PAMPs and DAMPs. (3) PAMPs and DAMPs bind Toll-like receptors and pathogen-recognition receptors, with subsequent cytokine and chemokine release. (4) Activation of the innate immune system with neutrophil recruitment and T-cell activation. (5) Resultant local and distant organ injury. MIP = macrophage inflammatory protein.
Figure 2.
Figure 2.
Schema of damage-associated molecular pattern (DAMP)- and pathogen-associated molecular pattern (PAMP)-mediated activation of innate immunity and inflammation. PAMPs and DAMPs released from infection and tissue injury, respectively, bind cell surface TLRs (Toll-like receptors) and PRRs (pattern-recognition receptors), leading to activation of NF-κB (nuclear factor-κB). NF-κB translocates to the nucleus and promotes expression of pro–IL-18, pro–IL1β, and NLRP3 (nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 3). NLRP3 is deubiquinated and combines with apoptosis-associated speck-like protein (ASC) and pro–caspase-1 to form the NLRP3 inflammasome. The activated NLRP3 inflammasome converts pro–caspase-1 to caspase-1. Caspase-1 subsequently then catalyzes the production of mature IL-18 and IL-1β. Iκ-B = inhibitor of κ-B; RAGE = receptor for advanced glycation end-products.
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