Pericytes facilitate leukocyte transmigration in vivo

Abstract

Venular walls are composed of endothelial cells, pericytes, and the vascular basement membrane (BM). Very little is known about the role of pericytes in leukocyte transmigration through venular walls. We have previously found that gaps between adjacent pericytes are co‐localised with matrix protein low expression regions (LERs) in the BM of murine cremasteric venules, regions that are preferentially used by transmigrating leukocytes to penetrate venular walls (Wang et al., J Exp Med., 2006). We now show that pericyte coverage determines the LERs expression profile in multiple other vascular beds, eg mesentery and skin. Furthermore, analysis of IL‐1b‐ or TNFa‐stimulated mouse cremaster muscles by immunofluorescence and confocal microscopy indicated the ability of these cytokines to induce contraction of pericytes in vivo (eg TNFa induced a 97% increase at 2h in the size of gaps between adjacent pericytes; p<0.001). Time‐course studies indicated that TNFa‐induced pericyte shape change preceded leukocyte transmigration. This response occurred independently of PMNs as it was also noted in PMN depleted mice. Collectively, the results demonstrate that pericytes facilitate leukocyte transmigration by governing the existence of leukocyte permissive regions in the vascular BM (ie LERs) and through active shape change at sites of inflammation. Funded by Barts & The London School of Medicine and The Wellcome Trust