Endothelial cell‐secreted MIF reduces pericyte contractility and enhances neutrophil extravasation

What is it about?

This work is the first to confirm that human pericytes are able to work with other cells of the vascular wall to control inflammatory recruitment of neutrophils into the tissue. Human pericytes are a contractile cell type that contribute to the formation of new vessels and stabilization of small vessels throughout our tissues. While we have come to understand how pericytes contribute to vascular support and stabilization, we have very little understanding of how they contribute to disease. Likewise, we have very little understanding of how singles are exchanged between the two major cell types of the vascular wall, in order to facilitate disease progression. Therefore, in this study we describe a mechanism by which human vascular wall pericytes form gaps through which human neutrophils can migrate from the blood stream and into the the tissue. The act of pericyte "relaxation", or release from the vascular wall, allows the pericyte to form gaps that make it easier for neutrophils to cross the vascular wall. What's more, human endothelial cells, the cells that line the interior of the vascular wall, are responsible for the primary signal that drives pericyte relaxation. When endothelial cells experience activation by a soluble inflammatory signal, they release a factor called Macrophage Inhibitory Factor, that binds to the receptors on pericytes, and allows them to relax. We demonstrate, in human models and in mice models of inflammation, that inhibition of this signaling pathway reduces neutrophil recruitment across the vascular wall and into the tissue.

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