title: Visualizing the neutrophil response to sterile tissue injury in mouse dermis reveals a three-phase cascade of events.
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.
authors.affiliation: The Centenary Institute, Newtown, New South Wales, Australia. Ng_Lai_Guan@immunol.a-star.edu.sg
authors.forename: Lai Guan
authors.initials: LG
authors.lastname: Ng
authors.forename: Jim S
authors.initials: JS
authors.lastname: Qin
authors.forename: Ben
authors.initials: B
authors.lastname: Roediger
authors.forename: Yilin
authors.initials: Y
authors.lastname: Wang
authors.forename: Rohit
authors.initials: R
authors.lastname: Jain
authors.forename: Lois L
authors.initials: LL
authors.lastname: Cavanagh
authors.forename: Adrian L
authors.initials: AL
authors.lastname: Smith
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Jones
authors.forename: Michael
authors.initials: M
authors.lastname: de Veer
authors.forename: Michele A
authors.initials: MA
authors.lastname: Grimbaldeston
authors.forename: Els N
authors.initials: EN
authors.lastname: Meeusen
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Weninger
mesh_terms: D000818:Animals; D002465:Cell Movement; D036563:Cyclic ADP-Ribose / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007249:Inflammation; D051379:Mice; D008810:Mice, Inbred C57BL; D008853:Microscopy / Q000379:methods; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism; D037342:Pertussis Toxin / Q000378:metabolism; D012756:Sheep; D012867:Skin / Q000276:immunology* / Q000473:pathology; D014945:Wound Healing
chemical_list: D036563:Cyclic ADP-Ribose; D049452:Green Fluorescent Proteins; D037342:Pertussis Toxin