Damage-Associated Molecular Patterns Control Neutrophil Recruitment

Neutrophils are recruited to a site of infection or injury where they help initiate the acute inflammatory response. In instances of sterile inflammation, where no microbial threats are present, this neutrophil recruitment is mediated by the release of danger signals or damage-associated molecular patterns (DAMPs) from disrupted cells and tissues. At basal state, many of these substances are sequestered and remain hidden within the cell, but are released following the rupture of the plasma membrane. In other instances, these DAMPs are undetected by the innate immune system unless chemically or proteolytically modified by tissue damage. DAMPs may be directly detected by neutrophils themselves and modulate their recruitment to sites of damage or, alternatively, they can act on other cell types which in turn facilitate the arrival of neutrophils to a site of injury. In this review, we outline the direct and indirect effects of a number of DAMPs, notably extracellular ATP, mitochondrial formylated peptides and mitochondrial DNA, all of which are released by necrotic cells. We examine the effect of these substances on the recruitment and behaviour of neutrophils to sites of sterile injury. We also highlight research which suggests that neutrophils are actively involved in triggering the resolution phase of an inflammatory response. This review brings to light a growing body of work that demonstrates that the release of DAMPs and the ensuing influx of neutrophils plays an important functional role in the inflammatory response, even when no pathogens are present.