Abstract
Upon tissue injury or microbial invasion, a large number of neutrophils converge from blood to the sites of injury or infection in a short time. The migration through a limited number of paths through tissues and capillary networks seems efficient and ‘traffic jams’ are generally avoided. However, the mechanisms that guide efficient trafficking of large numbers of neutrophils through capillary networks are not well understood. Here we show that pairs of neutrophils arriving closely one after another at capillary bifurcations migrate to alternating branches in vivo and in vitro. Perturbation of chemoattractant gradients and the increased hydraulic resistance induced by the first neutrophil in one branch biases the migration of the following neutrophil towards the other branch. These mechanisms guide neutrophils to efficiently navigate through capillary networks and outline the effect of inter-neutrophil interactions during migration on overall lymphocyte trafficking patterns in confined environments.
Highlights
Upon tissue injury or microbial invasion, a large number of neutrophils converge from blood to the sites of injury or infection in a short time
In mouse models of liver and lymph node, we find that consecutive neutrophils moving through capillaries toward sites of infection and injury take alternative routes more often than predicted by random decisions
We employed multiphoton microscopy and spinning-disk confocal intravital microscopy to observe the trafficking of neutrophils in capillary networks towards sites of tissue damage in the liver (N = 4 mice)
Summary
Upon tissue injury or microbial invasion, a large number of neutrophils converge from blood to the sites of injury or infection in a short time. Our results show that in the symmetrical bifurcation, the chance of consecutive neutrophils entering alternate branches are correlated with the cross-section of the channels as well as the distance between the two neutrophils in the squad. The second mechanism involves the alterations of the chemoattractant gradients in small channels by the moving neutrophils.
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