Cellular and molecular choreography of neutrophil recruitment to sites of sterile inflammation

Liberation of damage-associated molecular patterns (DAMPs) following tissue injury and necrotic cell death leads to the induction of sterile inflammation. A hallmark of acute inflammation is the recruitment of neutrophils to injured tissues. This review focuses on the journey of neutrophils to sites of sterile inflammation and the cellular and molecular mechanisms that choreograph this complex voyage. We review the pathway of leukocyte recruitment, with emphasis on recent additions to our understanding of intravascular neutrophil migration. The contributions of various tissue-resident sentinel cell populations to the detection of danger signals (DAMPs) and coordination of neutrophil recruitment and migration are discussed. In addition, we highlight recent data on the control of neutrophil chemotaxis towards sites of sterile inflammation, including new insight into the temporal and spatial regulation of chemoattractant guidance signals that direct cell migration. Given that inappropriate neutrophilic inflammation is a cornerstone in the pathogenesis of many diseases, a complete understanding of the choreography of neutrophil recruitment to sites of sterile inflammation may uncover new avenues for therapeutic interventions to treat inflammatory pathologies.