Pericytes support neutrophil subendothelial cell crawling and breaching of venular walls in vivo

Abstract

Neutrophil transmigration through venular walls that are composed of endothelial cells (ECs), pericytes, and the venular basement membrane is a key component of innate immunity. Through direct analysis of leukocyte-pericyte interactions in inflamed tissues using confocal intravital microscopy, we show how pericytes facilitate transmigration in vivo. After EC migration, neutrophils crawl along pericyte processes to gaps between adjacent pericytes in an ICAM-1-, Mac-1-, and LFA-1-dependent manner. These gaps were enlarged in inflamed tissues through pericyte shape change and were used as exit points by neutrophils in breaching the venular wall. The findings identify previously unknown roles for pericytes in neutrophil transmigration in vivo and add additional steps to the leukocyte adhesion cascade that supports leukocyte trafficking into sites of inflammation.