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Science. 2010 Oct 15;330(6002):362-6. doi: 10.1126/science.1195491.

Intravascular danger signals guide neutrophils to sites of sterile inflammation.

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  • 1Immunology Research Group, University of Calgary, Alberta T2N 4N1, Canada.

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  • Science. 2011 Mar 25;331(6024):1517.

Abstract

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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PMID:
20947763
[PubMed - indexed for MEDLINE]
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