Visualizing the neutrophil response to sterile tissue injury in mouse dermis reveals a three-phase cascade of events

Lai Guan Ng, Jim Qin, Ben Roediger, Yilin Wang, Rohit Jain, Lois Cavanagh, Adrian Smith, Cheryl Jones, Michael John de Veer, Michele Grimbaldeston, Elza Meeusen, Wolfgang Weninger

Research output: Contribution to journalArticleResearchpeer-review

110 Citations (Scopus)

Abstract

Neutrophil granulocytes traffic into sites of organ injury in which they may not only participate in tissue repair and pathogen clearance but may also contribute to collateral cell damage through the release of noxious mediators. The dynamics and mechanisms of neutrophil migration in the extravascular space toward loci of tissue damage are not well understood. Here, we have used intravital multi-photon microscopy to dissect the behavior of neutrophils in response to tissue injury in the dermis of mice. We found that, following confined physical injury, initially rare scouting neutrophils migrated in a directional manner toward the damage focus. This was followed by the attraction of waves of additional neutrophils, and finally stabilization of the neutrophil cluster around the injury. Although neutrophil migration in the steady state and during the scouting phase depended on pertussis toxin-sensitive signals, the amplification phase was sensitive to interference with the cyclic adenosine diphosphate ribose pathway. We finally demonstrated that neutrophil scouts also transit through the non-inflamed dermis, suggesting immunosurveillance function by these cells. Together, our data unravel a three-step cascade of events that mediates the specific accumulation of neutrophils at sites of sterile tissue injury in the interstitial space.
Original languageEnglish
Pages (from-to)2058 - 2068
Number of pages11
JournalJournal of Investigative Dermatology
Volume131
Issue number10
DOIs
Publication statusPublished - 2011

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