Intravascular danger signals guide neutrophils to sites of sterile inflammation
PainSci summary of McDonald 2010?This page is one of thousands in the PainScience.com bibliography. It is not a general article: it is focused on a single scientific paper, and it may provide only just enough context for the summary to make sense. Links to other papers and more general information are provided at the bottom of the page, as often as possible. ★★★★★?5-star ratings are for sentinel studies, excellent experiments with meaningful results. Ratings are a highly subjective opinion, and subject to revision at any time. If you think this paper has been incorrectly rated, please let me know.
Researchers at the University of Calgary Faculty of Medicine are using an innovative new imaging technique to study how white blood cells (called neutrophils) respond to inflammation, and have revealed new targets to inhibit the response. Basically this research explains why neutrophils unnecessarily “swarm” sterile injury sites, causing damage and pain with no direct benefit — a biological glitch with profound implications. Collateral damage!
original abstract†Abstracts here may not perfectly match originals, for a variety of technical and practical reasons. Some abstacts are truncated for my purposes here, if they are particularly long-winded and unhelpful. I occasionally add clarifying notes. And I make some minor corrections.
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.
related content
Specifically regarding McDonald 2010:
- PS Why Does Pain Hurt? — How an evolutionary wrong turn led to a biological glitch that condemned the animal kingdom — you included — to much louder, longer pain
- “Images shed new light on inflammation,” Braedon McDonald and Paul Kubes, Faculty of Medicine (University of Calgary).
“Immune Collateral Damage: An interview with Paul Kubes” an audio recording from Quirks & Quarks (CBC Radio One).
These three articles on PainScience.com cite McDonald 2010 as a source:
- PS 34 Surprising Causes of Pain — Trying to understand pain when there is no obvious explanation
- PS Tissue Provocation Therapies — Can healing be forced? The laws of tissue adaptation & therapies like prolotherapy & Graston Technique
This page is part of the PainScience BIBLIOGRAPHY, which contains plain language summaries of thousands of scientific papers & others sources. It’s like a highly specialized blog. A few highlights:
- Effectiveness of customised foot orthoses for Achilles tendinopathy: a randomised controlled trial. Munteanu 2015 Br J Sports Med.
- A Bayesian model-averaged meta-analysis of the power pose effect with informed and default priors: the case of felt power. Gronau 2017 Comprehensive Results in Social Psychology.
- The neck and headaches. Bogduk 2014 Neurol Clin.
- Agreement of self-reported items and clinically assessed nerve root involvement (or sciatica) in a primary care setting. Konstantinou 2012 Eur Spine J.
- Effect of NSAIDs on Recovery From Acute Skeletal Muscle Injury: A Systematic Review and Meta-analysis. Morelli 2017 Am J Sports Med.