Pré-Publication, Document De Travail Année : 2025

Adaptive motility enables neutrophils to rapidly navigate confined capillaries

Mathieu Maurin

Résumé

As the first responders of the immune system, neutrophils rapidly and abundantly reach inflamed tissues through blood capillaries. The diameter of capillaries can be as narrow as two microns, imposing considerable deformations on neutrophils. Notably, capillary obstruction due to neutrophil retention causes vascular dysfunction and contributes to the pathogenesis of several diseases. However, the cellular mechanisms that allow neutrophils to migrate into small capillaries and to avoid retention remain unknown. In this study, we demonstrate, both in vivo and in vitro , that capillary size does not influence neutrophil migration velocity. During migration into capillaries of different sizes, neutrophils maintain high speed, a phenomenon associated with a global actomyosin cytoskeleton rearrangement in response to confinement strength. In irregular capillaries, neutrophils rapidly adapt their cell contractility via the ROCK-MyoII pathway, which allows them to sustain their migration speed along the vessels despite changes in confinement. At the single cell level, inhibition of ROCK impairs actomyosin cytoskeleton rearrangement and reduces neutrophil migration speed within confined capillaries. At the collective level, ROCK inhibition hampers efficient neutrophil trafficking in a network of small capillaries, resulting in vessel obstruction. These findings reveal a unique capacity of neutrophils to rapidly and dynamically adapt their migration to the confinement strength of capillaries, an ability that might limit vascular dysfunction during inflammation.

Fichier principal
Vignette du fichier
2025.01.08.631737v2.full.pdf (17.19 Mo) Télécharger le fichier
Origine Fichiers produits par l'(les) auteur(s)
Licence

Dates et versions

hal-05401067 , version 1 (05-12-2025)

Licence

Identifiants

Citer

Mathieu Deygas, Mathilde Bernard, Pierre Nivoit, Lucie Barbier, Li Wang, et al.. Adaptive motility enables neutrophils to rapidly navigate confined capillaries. 2025. ⟨hal-05401067⟩
1269 Consultations
175 Téléchargements

Altmetric

Partager

  • More