The grateful dead: damage-associated molecular pattern molecules and reduction/oxidation regulate immunity
Article first published online: 30 OCT 2007
Volume 220, Issue 1, pages 60–81, December 2007
How to Cite
Lotze, M. T., Zeh, H. J., Rubartelli, A., Sparvero, L. J., Amoscato, A. A., Washburn, N. R., DeVera, M. E., Liang, X., Tör, M. and Billiar, T. (2007), The grateful dead: damage-associated molecular pattern molecules and reduction/oxidation regulate immunity. Immunological Reviews, 220: 60–81. doi: 10.1111/j.1600-065X.2007.00579.x
- Issue published online: 30 OCT 2007
- Article first published online: 30 OCT 2007
Summary: The response to pathogens and damage in plants and animals involves a series of carefully orchestrated, highly evolved, molecular mechanisms resulting in pathogen resistance and wound healing. In metazoans, damage- or pathogen-associated molecular pattern molecules (DAMPs, PAMPs) execute precise intracellular tasks and are also able to exert disparate functions when released into the extracellular space. The emergent consequence for both inflammation and wound healing of the abnormal extracellular persistence of these factors may underlie many clinical disorders. DAMPs/PAMPs are recognized by hereditable receptors including the Toll-like receptors, the NOD1-like receptors and retinoic-acid-inducible gene I-like receptors, as well as the receptor for advanced glycation end products. These host molecules ‘sense’ not only pathogens but also misfolded/glycated proteins or exposed hydrophobic portions of molecules, activating intracellular cascades that lead to an inflammatory response. Equally important are means to not only respond to these molecules but also to eradicate them. We have speculated that their destruction through oxidative mechanisms normally exerted by myeloid cells, such as neutrophils and eosinophils, or their persistence in the setting of pathologic extracellular reducing environments, maintained by exuberant necrotic cell death and/or oxidoreductases, represent important molecular means enabling chronic inflammatory states.