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

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

After transendothelial cell migration, neutrophils actively crawl along pericyte processes before exiting the venular wall via selected gaps between adjacent pericytes.

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.

Related collections

Most cited references 35

Record: found
Abstract: found
Article: not found

Neutrophil serine proteases: specific regulators of inflammation.

Christine Pham (2006)

Neutrophils are essential for host defence against invading pathogens. They engulf and degrade microorganisms using an array of weapons that include reactive oxygen species, antimicrobial peptides, and proteases such as cathepsin G, neutrophil elastase and proteinase 3. As discussed in this Review, the generation of mice deficient in these proteases has established a role for these enzymes as intracellular microbicidal agents. However, I focus mainly on emerging data indicating that, after release, these proteases also contribute to the extracellular killing of microorganisms, and regulate non-infectious inflammatory processes by activating specific receptors and modulating the levels of cytokines.

0 comments Cited 294 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Pericytes in the microvasculature.

K Hirschi, P D'Amore (1996)

Pericytes, also known as Rouget cells or mural cells, are associated abluminally with all vascular capillaries and post-capillary venules. Differences in pericyte morphology and distribution among vascular beds suggest tissue-specific functions. Based on their location and their complement of muscle cytoskeletal proteins, pericytes have been proposed to play a role in the regulation of blood flow. In vitro studies demonstrating the contractile ability of pericytes support this concept. Pericytes have also been suggested to be oligopotential and have been reported to differentiate into adipocytes, osteoblasts and phagocytes. The mechanisms involved in vessel formation have yet to be elucidated but observations indicate that the primordial endothelium can recruit undifferentiated mesenchymal cells and direct their differentiation into pericytes in microvessels, and smooth muscle cells in large vessels. Communication between endothelial cells and pericytes, or their precursors, may take many forms. Soluble factors such as platelet-derived growth factor and transforming growth factors-beta are likely to be involved. In addition, physical contact mediated by cell adhesion molecules, integrins and gap junctions appear to contribute to the control of vascular growth and function. Development of culture methods has allowed some functions of pericytes to be directly examined. Co-culture of pericytes with endothelial cells leads to the activation of transforming growth factor-beta, which in turn influences the growth and differentiation of the vascular cells. Finally, the pericyte has been implicated in the development of a variety of pathologies including hypertension, multiple sclerosis, diabetic microangiopathy and tumor vascularization.

0 comments Cited 138 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Venular basement membranes contain specific matrix protein low expression regions that act as exit points for emigrating neutrophils

Shijun Wang, Mathieu-Benoit Voisin, Karen Y. Larbi … (2006)

The mechanism of leukocyte migration through venular walls in vivo is largely unknown. By using immunofluorescence staining and confocal microscopy, the present study demonstrates the existence of regions within the walls of unstimulated murine cremasteric venules where expression of key vascular basement membrane (BM) constituents, laminin 10, collagen IV, and nidogen-2 (but not perlecan) are considerably lower (<60%) than the average expression detected in the same vessel. These sites were closely associated with gaps between pericytes and were preferentially used by migrating neutrophils during their passage through cytokine-stimulated venules. Although neutrophil transmigration did not alter the number/unit area of extracellular matrix protein low expression sites, the size of these regions was enlarged and their protein content was reduced in interleukin-1β–stimulated venules. These effects were entirely dependent on the presence of neutrophils and appeared to involve neutrophil-derived serine proteases. Furthermore, evidence was obtained indicating that transmigrating neutrophils carry laminins on their cell surface in vivo. Collectively, through identification of regions of low extracellular matrix protein localization that define the preferred route for transmigrating neutrophils, we have identified a plausible mechanism by which neutrophils penetrate the vascular BM without causing a gross disruption to its intricate structure.

0 comments Cited 101 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): J Exp Med

Journal ID (iso-abbrev): J. Exp. Med

Journal ID (hwp): jem

Title: The Journal of Experimental Medicine

Publisher: The Rockefeller University Press

ISSN (Print): 0022-1007

ISSN (Electronic): 1540-9538

Publication date (Print): 4 June 2012

Volume: 209

Issue: 6

Pages: 1219-1234

Affiliations

[1 ]William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK

[2 ]Randall Division, King’s College London, Guy’s Campus, London SE1 1UL, UK

[3 ]Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030

Author notes

CORRESPONDENCE Sussan Nourshargh: s.nourshargh@ 123456qmul.ac.uk

D. Proebstl and M.B. Voisin contributed equally to this paper.

Article

Publisher ID: 20111622

DOI: 10.1084/jem.20111622

PMC ID: 3371725

PubMed ID: 22615129

SO-VID: ab0be8cb-abb6-4c4d-90fb-a0fdb1b6eac1

License:

This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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

Read this article at

Abstract

Abstract

Related collections

Gamma Delta T cells

Most cited references 35

Neutrophil serine proteases: specific regulators of inflammation.

Pericytes in the microvasculature.

Venular basement membranes contain specific matrix protein low expression regions that act as exit points for emigrating neutrophils

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 44

Cited by 161

Most referenced authors 1,211