Publication Date:
2013-05-28
Description:
Neutrophil recruitment from blood to extravascular sites of sterile or infectious tissue damage is a hallmark of early innate immune responses, and the molecular events leading to cell exit from the bloodstream have been well defined. Once outside the vessel, individual neutrophils often show extremely coordinated chemotaxis and cluster formation reminiscent of the swarming behaviour of insects. The molecular players that direct this response at the single-cell and population levels within the complexity of an inflamed tissue are unknown. Using two-photon intravital microscopy in mouse models of sterile injury and infection, we show a critical role for intercellular signal relay among neutrophils mediated by the lipid leukotriene B4, which acutely amplifies local cell death signals to enhance the radius of highly directed interstitial neutrophil recruitment. Integrin receptors are dispensable for long-distance migration, but have a previously unappreciated role in maintaining dense cellular clusters when congregating neutrophils rearrange the collagenous fibre network of the dermis to form a collagen-free zone at the wound centre. In this newly formed environment, integrins, in concert with neutrophil-derived leukotriene B4 and other chemoattractants, promote local neutrophil interaction while forming a tight wound seal. This wound seal has borders that cease to grow in kinetic concert with late recruitment of monocytes and macrophages at the edge of the displaced collagen fibres. Together, these data provide an initial molecular map of the factors that contribute to neutrophil swarming in the extravascular space of a damaged tissue. They reveal how local events are propagated over large-range distances, and how auto-signalling produces coordinated, self-organized neutrophil-swarming behaviour that isolates the wound or infectious site from surrounding viable tissue.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3879961/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3879961/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lammermann, Tim -- Afonso, Philippe V -- Angermann, Bastian R -- Wang, Ji Ming -- Kastenmuller, Wolfgang -- Parent, Carole A -- Germain, Ronald N -- ZIA AI000545-24/Intramural NIH HHS/ -- England -- Nature. 2013 Jun 20;498(7454):371-5. doi: 10.1038/nature12175. Epub 2013 May 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-0421, USA. laemmermannt@niaid.nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23708969" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cell Death
;
Chemotactic Factors/immunology/*metabolism
;
*Chemotaxis, Leukocyte/immunology
;
Collagen/metabolism
;
Female
;
Immunity, Innate
;
Integrins/*metabolism
;
Leukotriene B4/immunology/*metabolism
;
Lymph Nodes/cytology/immunology
;
Macrophages/cytology/microbiology/pathology
;
Male
;
Mice
;
*Neutrophil Infiltration
;
Neutrophils/*cytology/physiology
;
Pseudomonas aeruginosa/pathogenicity
;
Receptors, G-Protein-Coupled/metabolism
;
Skin/cytology/injuries/pathology
;
Wound Healing/*physiology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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