Systemic Inflammation and Acute-on-Chronic Liver Failure: Too Much, Not Enough

Table 2

Examples of well-characterized DAMPs (danger signals or alarmins).

DAMPs	Receptors	Outcome of receptor ligation
Extracellular nucleotides (ATP, ADP, adenosine)	PI, P2X, and P2Y receptors (ATP, ADP); Al, A2A, A2B, and A3 receptors (adenosine)	Dendritic cell (DC) maturation, chemotaxis, secretion of cytokines (IL-1β, IL-18), inflammation
Extracellular heat shock proteins	CD14, CD91, scavenger receptors, TLR4, TLR2, CD40	DC maturation, cytokine induction, DC, migration to lymph nodes
Extracellular HMGB1	RAGE, TLR2, TLR4	Chemotaxis, cytokine induction, DC activation, neutrophil recruitment, inflammation, activation of immune cells
Uric acid crystals	CD14, TLR2, TLR4	DC activation, cytokine induction, neutrophil recruitment, gout induction
Laminin	Integrins	Neutrophil recruitment, chemotaxis
S100 proteins or calgranulins	RAGE	Neutrophil recruitment, chemotaxis, cytokine secretion, apoptosis
Hyaluronan	TLR2, TLR4, CD44	DC maturation, cytokine production, adjuvant activity
IL-1 family
IL-1α	IL1R1 and IL1RAP	Inflammatory; promotes activation, costimulation, and secretion of cytokines and other acute-phase proteins; pyrogenic
IL-33	IL1RL1 and IL1RAP	Inducer of type 2 immune responses, activating T helper 2 (TH2) cells and mast cells; stimulates group 2 innate lymphoid cells (ILC2s), regulatory T (Treg) cells, TH1 cells, CD8+ T cells and natural killer (NK) cells.
Mitochondrial DAMPs
mtDNA	TLR9	Proinflammatory cytokines, neutrophil chemoattraction and matrix metalloproteinase secretion, type I IFN responses 91
N-Formylated peptides	FPR	Neutrophil chemoattraction