Prof. Sussan Nourshargh, Leukocyte motility through venular walls in vivo
Date: Wed 18 Sep 2013, 15:00 - 16:00
Location: The People's Palace - PP1
William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
SEMS/IoB Seminar Series
Coffee/tea/biscuits provided after the seminar
Leukocyte motility through venular walls in vivo
Migration of leukocytes to sites of injury or inflammation is a crucial component of both innate and adaptive immunity. To penetrate venular walls, leukocytes must migrate through multiple barriers, endothelial cells (EC), the pericyte sheath and the venular basement membrane (BM)1 . Although there is increasing interest and understanding of the mechanisms that mediate transendothelial cell migration (TEM), the relative contribution of individual molecules requires further clarification1;2. Within our group we aim to investigate the mechanisms of leukocyte transmigration through imaging of inflamed tissues by multiple methods, including the application of high resolution confocal intravital microscopy. With this approach we have characterised the profile and dynamics of different modes of leukocyte transmigration through venular walls and have obtained evidence for differential roles of different EC junctional molecules in this process, including a role for JAM-C in regulation of polarised luminal to abluminal neutrophil TEM3;4. Our studies have also shed light on the mechanisms through which leukocytes breach the venular basement membrane and the pericyte sheath5-7. Collectively, through rigorous analysis of leukocyte-vessel wall interactions by direct real-time imaging of inflamed tissues, our findings provide novel insights into the cellular and molecular mechanism via which leukocytes cross the venular walls in vivo.
Funded by The Wellcome Trust.
1. Nourshargh S, Hordijk PL, Sixt M. Breaching multiple barriers: leukocyte motility through venular walls and the interstitium. Nat Rev Mol Cell Biol (2010), 11:366-378.
2. Ley, K., Laudanna, C., Cybulsky, M. I., and Nourshargh, S. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nature Reviews Immunology (2007), 7:678-689.
3. Woodfin A, Voisin MB, Beyrau M et al. The junctional adhesion molecule JAM-C regulates polarized transendothelial migration of neutrophils in vivo. Nat Immunol (2011), 12:761-769.
4. Woodfin A, Voisin MB, Imhof BA et al. Endothelial cell activation leads to neutrophil transmigration as supported by the sequential roles of ICAM-2, JAM-A and PECAM-1. Blood (2009), 113:6246-6257.
5. Wang S, Voisin M-B, Larbi KY et al. Venular basement membranes contain specific matrix protein low expression regions that act as exit points for emigrating PMN. J Exp Med (2006), 203:1519-1532.
6. Voisin MB, Probstl D, Nourshargh S. Venular basement membranes ubiquitously express matrix protein low-expression regions: Characterization in multiple tissues and remodeling during inflammation. Am J Pathol (2010), 176:482-495.
7. Proebstl D., Voisin M-B., Woodfin A., Whiteford J., D’Acquisto F., Jones G., Rowe D. & Nourshargh S.
Pericytes support neutrophil sub-endothelial cell crawling and breaching of venular walls in vivo.
J Exp Med., (2012), 209:1219-1234.
Updated by: Jonathon Hills