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Three-dimensional forces exerted by leukocytes and vascular endothelial cells dynamically facilitate diapedesis

Leukocyte transmigration across vessel walls is a critical step in the innate immune response. Upon their activation and firm adhesion to vascular endothelial cells (VECs), leukocytes preferentially extravasate across junctional gaps in the endothelial monolayer (paracellular diapedesis). It has bee...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2018-01, Vol.115 (1), p.133-138
Main Authors: Yeh, Yi-Ting, Serrano, Ricardo, François, Joshua, Chiu, Jeng-Jiann, Li, Yi-Shuan Julie, del Álamo, Juan C., Chien, Shu, Lasheras, Juan C.
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cited_by cdi_FETCH-LOGICAL-c509t-21282f0c7c7520a72b7be5c8bac0b278eb6ed9f0751d80bcf25e7ab311935b53
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container_title Proceedings of the National Academy of Sciences - PNAS
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creator Yeh, Yi-Ting
Serrano, Ricardo
François, Joshua
Chiu, Jeng-Jiann
Li, Yi-Shuan Julie
del Álamo, Juan C.
Chien, Shu
Lasheras, Juan C.
description Leukocyte transmigration across vessel walls is a critical step in the innate immune response. Upon their activation and firm adhesion to vascular endothelial cells (VECs), leukocytes preferentially extravasate across junctional gaps in the endothelial monolayer (paracellular diapedesis). It has been hypothesized that VECs facilitate paracellular diapedesis by opening their cell–cell junctions in response to the presence of an adhering leukocyte. However, it is unclear how leukocytes interact mechanically with VECs to open the VEC junctions and migrate across the endothelium. In this study, we measured the spatial and temporal evolution of the 3D traction stresses generated by the leukocytes and VECs to elucidate the sequence of mechanical events involved in paracellular diapedesis. Our measurements suggest that the contractile stresses exerted by the leukocytes and the VECs can separately perturb the junctional tensions of VECs to result in the opening of gaps before the initiation of leukocyte transmigration. Decoupling the stresses exerted by the transmigrating leukocytes and the VECs reveals that the leukocytes actively contract the VECs to open a junctional gap and then push themselves across the gap by generating strong stresses that push into the matrix. In addition, we found that diapedesis is facilitated when the tension fluctuations in the VEC monolayer were increased by proinflammatory thrombin treatment. Our findings demonstrate that diapedesis can be mechanically regulated by the transmigrating leukocytes and by proinflammatory signals that increase VEC contractility.
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subjects Biological Sciences
Cell activation
Cell adhesion & migration
Cell junctions
Cells
Contractility
Decoupling
Diapedesis
Endothelial cells
Endothelium
Extravasation
HL-60 Cells
Human Umbilical Vein Endothelial Cells - cytology
Human Umbilical Vein Endothelial Cells - metabolism
Humans
Immune response
Immune system
Inflammation
Innate immunity
Intercellular Junctions - metabolism
Leukocyte migration
Leukocytes
Leukocytes - cytology
Leukocytes - metabolism
Medical treatment
Models, Biological
Monolayers
Stresses
Thrombin
Transendothelial and Transepithelial Migration - physiology
title Three-dimensional forces exerted by leukocytes and vascular endothelial cells dynamically facilitate diapedesis
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