DAMPS or danger-associated molecular patterns are intracellular components which also induce TLR dependent inflammatory responses.
Types of DAMPS
High mobility group 1 protein (HMGB1): is an intracellular protein that can translocate to the nucleus and act as a transcription factor. When released by activated monocytes, it participates in the development of lethality and activates downstream cytokine release. As a proinflammatory cytokine HMGB1 is lethal to otherwise healthy animals. Elevated levels of HMGB1 were observed in the serum of patients with sepsis. The mechanism of action is binding to TLR4 which activates macrophage cytokine release.
Heat shock proteins (HSP) HSP70 and HSP90, and cellular RNA released during cellular injury, also induce TLR-dependent inflammatory responses.
DAMP Inhibitors:
(1) CD24: deficient mice exhibit increased susceptibility to danger but not pathogen-associated molecular patterns. CD24 associates with high mobility group box 1 (HMGB1), HSP70 and HSP90, which negatively regulates their stimulatory activity and inhibits nuclear factor kappa B activation. This occurs at least in part through CD24 association with Siglec-10 in humans or Siglec-G in mice. Results from one group show that the CD24-Siglec G (or Siglec-10 in humans) pathway protects the host against a lethal response to pathological cell death and discriminates danger asssociated versus pathogen-associated molecular patterns. CD24 and Siglec-10/G appear to be selective modulators of the host response to HMGB1, but not to TLR ligands such as LPS. See US Patent Applicaiton 12/716842.