Publication Date:
2010-10-16
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McDonald, Braedon -- Pittman, Keir -- Menezes, Gustavo B -- Hirota, Simon A -- Slaba, Ingrid -- Waterhouse, Christopher C M -- Beck, Paul L -- Muruve, Daniel A -- Kubes, Paul -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2010 Oct 15;330(6002):362-6. doi: 10.1126/science.1195491.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immunology Research Group, University of Calgary, Alberta T2N 4N1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20947763" target="_blank"〉PubMed〈/a〉
Keywords:
Adenosine Triphosphate/metabolism
;
Animals
;
Carrier Proteins/metabolism
;
Cell Adhesion
;
Chemokine CXCL2/metabolism
;
Chemokines/metabolism
;
Chemotaxis, Leukocyte
;
Cues
;
Endothelium, Vascular/physiology
;
Inflammation/*immunology/metabolism/*pathology
;
Kinetics
;
Liver/blood supply/*immunology/metabolism/*pathology
;
Liver Diseases/*immunology/metabolism/*pathology
;
Macrophage-1 Antigen/physiology
;
Mice
;
Microscopy/methods
;
Microscopy, Confocal
;
Microvessels/physiology
;
Necrosis
;
*Neutrophil Infiltration
;
Neutrophils/physiology
;
Peptides/metabolism
;
Receptors, Formyl Peptide/metabolism
;
Receptors, Interleukin-8B/metabolism
;
Receptors, Purinergic P2/metabolism
;
Receptors, Purinergic P2X7
;
Signal Transduction
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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