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Damage Associated Molecular Patterns (DAMPS)
From Sci-Mate WikiBiological and Medical Sciences > Classification by Discipline > Immunology
Type: General Knowledge
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22.04.2010 - Christopher Dyer - Sci-Mate
Damage Associated Molecular Patterns (DAMPs) are immunologically relevant 'danger signals' released following specific forms of cell death causing inflammation and activation of APCs and lymphocytes (originally hypothesised, (Matzinger, 1994); egs, (Ma et al., 2005; Rohn et al., 2005); reviewed, (Kono et al., 2008)). DAMPS are derived from pre-existing molecules (Shi et al., 2000) released through membrane rupture, as in the case of Necrosis, or Proptosis (reviewed (Bergsbaken et al., 2009)), or from within inflammasomes (reviewed (Franchi et al., 2009)). Excessive signalling from DAMPs has been shown to contribute to allergic and autoimmune activity (missing ref.), and currently, the presence of uric acid (a DAMP, see below) is being investigated in rheumatoid arthritis (missing ref.). Obviously- understanding the role of these molecules in the immunological response to cell death shall be relevant to many diseases and treatments.
 Candidate DAMPs
Several molecules, which might be expected to be released following necrosis, including uric acid (Shi et al., 2003) and heat-shock proteins (HSPs) (Binder et al., 2000; Udono and Srivastava, 1993), have been shown to enhance both cellular activation, and inflammation.
 Candidate Receptors and Signalling Pathways
Surprisingly, studies using TLR-deficient mice showed that DAMP inflammation is not dependent on any single TLR, although mice deficient in both TLR2 and TLR4 did show minor reductions in inflammation, and TLR5 and TLR8 were not tested (Chen et al., 2007).
CLEC9A has been reported to provide stimulation for dead-cell associated antigens via SYK signalling, thereby implicating the SRC family of kinases (Sancho et al., 2009). Previously, other SYK-coupled C-type lectins have been implicated in inflammatory responses to necrotic cells (Yamasaki et al., 2008; Ziegenfuss et al., 2008), so this latest finding represents a critical step forward that will likely stimulate considerable interest and ongoing research.
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