Neutrophil Swarming in Damaged Tissue Is Orchestrated by Connexins and Cooperative Calcium Alarm Signals
| Autor: | Morgane Boulch, Foteini Papaleonidopoulou, Antonios Georgantzoglou, Hazel A. Walker, Hugo Poplimont, Caroline Coombs, Milka Sarris |
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| Přispěvatelé: | Poplimont, Hugo [0000-0002-2319-363X], Sarris, Milka [0000-0001-7016-333X], Apollo - University of Cambridge Repository |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Leukocyte migration Leukotriene B4 Neutrophils wound Inflammation General Biochemistry Genetics and Molecular Biology Connexins 03 medical and health sciences Paracrine signalling chemistry.chemical_compound 0302 clinical medicine Adenosine Triphosphate Live cell imaging Calcium flux medicine Animals chemotaxis Zebrafish Cell Aggregation biology leukotriene tissue damage Chemotaxis biology.organism_classification infection swarming Cell biology leukocyte migration 030104 developmental biology chemistry Neutrophil Infiltration inflammation Connexin 43 Pseudomonas aeruginosa Wounds and Injuries Calcium medicine.symptom General Agricultural and Biological Sciences 030217 neurology & neurosurgery Signal Transduction |
| DOI: | 10.17863/cam.52713 |
| Popis: | Summary Neutrophils are major inflammatory cells that rapidly infiltrate wounds to provide antimicrobial functions. Within the damaged tissue, neutrophil migration behavior often switches from exploratory patrolling to coordinated swarming, giving rise to dense clusters that further disrupt tissue architecture. This aggregation response is self-organized by neutrophil paracrine chemoattractant signaling (most notably of the inflammatory mediator leukotriene B4 [LTB4]). The coordination mechanism and possible evolutionary benefits of neutrophil swarms are elusive. Here, we show that neutrophil swarms require mutual reinforcement of damage signaling at the wound core. New biosensors and live imaging in zebrafish revealed that neutrophil chemoattractant synthesis is triggered by a sustained calcium flux upon contact with necrotic tissue that requires sensing of the damage signal ATP. This “calcium alarm” signal rapidly propagates in the nascent neutrophil cluster in a contact-dependent manner via connexin-43 (Cx43) hemichannels, which are mediators of active ATP release. This enhances chemoattractant biosynthesis in the growing cluster, which is instrumental for coordinated motion and swarming. Inhibition of neutrophil Cx43 compromises clearance of wound-colonizing P. aeruginosa bacteria and exacerbates infection-induced morbidity. Thus, cooperative production of alarm signals among pioneer clustering neutrophils fuels the growth of dense antimicrobial cell masses that effectively seal off breached tissue barriers from opportunistic pathogens. |
| Databáze: | OpenAIRE |
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