Journal Article

Breaching multiple barriers: leukocyte motility through venular walls and the interstitium

Hordijk, Peter L., Sixt, Michael, Nourshargh, Sussan

2010

Overview

Key Points The shuttling of leukocytes between the blood stream and interstitial tissues involves different locomotion strategies that are governed by locally presented soluble and cell-bound signals. There are key concepts in the regulation of leukocyte migration through venular walls and motility in the extravascular tissue, with common and distinct mechanisms mediating these responses. Integrin-mediated adhesion of leukocytes to endothelial cells lining venular walls is a prerequisite to leukocyte crawling over and migration through endothelial cells. These responses are associated with great morphological changes in both leukocytes and endothelial cells and can support leukocyte transendothelial cell migration through both paracellular and transcellular routes. Leukocyte migration through endothelial cells is dependent on signalling events in both leukocytes and endothelial cells, events that can regulate leukocyte–endothelial cell interactions, as well as contacts between adjacent endothelial cells and/or endothelial cell vesicular trafficking. After endothelial cell migration, leukocytes need to penetrate the pericyte sheath and the venular basement membrane in which pericytes are embedded. Breaching the pericyte layer may occur through gaps between adjacent cells or in a transcellular manner. Migration through the venular basement membrane occurs through regions that may be biochemically or biophysically permissive. Once detached from the perivascular basement membrane, leukocytes approach their final destination by crawling within the three-dimensional interstitial space, which can either be a fibrillar network or a cell-packed environment like many organ parenchymas or lymphatic tissues. Leukocyte migration in the interstitium is driven by actin protrusion at the leading edge and is occasionally supported by actomyosin contraction at the trailing edge. The cytoskeletal forces can be transduced onto the environment either by integrins or by direct physical interaction of the cell body with the extracellular environment. This flexible mode of migration renders leukocytes largely independent of the molecular composition of the interstitium. Leukocytes use different strategies to migrate through the endothelium of venular walls and in interstitial tissues. These strategies are regulated by soluble and cell-bound signals. Studies have identified many of the cellular and subcellular events that govern transendothelial migration and are beginning to elucidate the nature of leukocyte interstitial motility. The shuttling of leukocytes between the bloodstream and interstitial tissues involves different locomotion strategies that are governed by locally presented soluble and cell-bound signals. Recent studies have furthered our understanding of the rapidly advancing field of leukocyte migration, particularly regarding cellular and subcellular events at the level of the venular wall. Furthermore, emerging cellular models are now addressing the transition from an adherent mode to a non-adherent state, incorporating mechanisms that support an efficient migratory profile of leukocytes in the interstitial tissue beyond the venular wall.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/443/1338 / 631/80/84 / 631/80/86 / 692/698/1543/1565/1597 / Animals / Basement Membrane - cytology / Basement Membrane - metabolism / Biochemistry / Biomedical and Life Sciences / Blood vessels / Cancer Research / Cell Biology / Cell migration / Cell Movement / Cells / Chemokines / Cytokines / Developmental Biology / Endothelial Cells - cytology / Endothelial Cells - metabolism / Endothelium / Humans / Leukocytes / Leukocytes - cytology / Leukocytes - metabolism / Life Sciences / Microscopy / Motility / Pericytes - cytology / Pericytes - metabolism / Properties / review-article / Stem Cells / Venules - cytology / Venules - metabolism