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Publication : Intravascular danger signals guide neutrophils to sites of sterile inflammation.

First Author  McDonald B Year  2010
Journal  Science Volume  330
Issue  6002 Pages  362-6
PubMed ID  20947763 Mgi Jnum  J:164871
Mgi Id  MGI:4835577 Doi  10.1126/science.1195491
Citation  McDonald B, et al. (2010) Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science 330(6002):362-6
abstractText  Neutrophils are recruited from the blood to sites of sterile inflammation, where they contribute to wound healing but may also cause tissue damage. By using spinning disk confocal intravital microscopy, we examined the kinetics and molecular mechanisms of neutrophil recruitment to sites of focal hepatic necrosis in vivo. Adenosine triphosphate released from necrotic cells activated the Nlrp3 inflammasome to generate an inflammatory microenvironment that alerted circulating neutrophils to adhere within liver sinusoids. Subsequently, generation of an intravascular chemokine gradient directed neutrophil migration through healthy tissue toward foci of damage. Lastly, formyl-peptide signals released from necrotic cells guided neutrophils through nonperfused sinusoids into the injury. Thus, dynamic in vivo imaging revealed a multistep hierarchy of directional cues that guide neutrophil localization to sites of sterile inflammation.
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