© 2003 Schattauer GmbH, Stuttgart Review Article 598 Introduction Migration of leukocytes to sites of injury or inflammation is a crucial component of both innate and adaptive immunity. To achieve this, finely co-ordinated mechanisms exist by which intravascular leukocytes are able to penetrate the vascular wall and migrate to sites of injury or infection without causing any perceptible damage to the vessels from which they emigrate. Within this scenario, leukocyte transmigration through vessel walls (predominantly post-capillary venules) is the final stage of a stepwise cascade of leukocyte responses mediated by a series of sequential molecular interactions that initially mediate the slowing down of leukocyte rolling velocity followed by leu- kocyte firm adhesion to the endothelium and eventually migra- tion through the vessel wall (Fig. 1). As illustrated and dis- cussed in this review, leukocyte transmigration not only acts as a means of directing the emigration of leukocytes from the vas- cular lumen to the extravascular tissue but may also play a crit- ical role in regulating the phenotype of the emigrated cells such that leukocyte behaviour in the form of responsiveness to chemoattractants, directional migration and interactions with components of the extravascular tissue may be regulated. Such Migration of leukocytes through the vessel wall and beyond Rashmi Yadav, Karen Y. Larbi, Rebecca E.Young, Sussan Nourshargh Cardiovascular Medicine Unit, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, United Kingdom Thromb Haemost 2003; 90: 598 – 606 employed to investigate leukocyte migration in vivo, focuses primarily on mechanisms of leukocyte transmigration, the final step in the process of leukocyte emigration. Furthermore, special emphasis is placed on discussing the process and the mechanisms involved in leukocyte migration through the base- ment membrane, a structure that presents significant impe- dance to transmigrating leukocytes but is seldom investigated in the context of leukocyte transmigration in vivo.The review also discusses the growing evidence supporting the concept that leukocyte transmigration is not only a response that describes the passage of leukocytes through the venular wall, but also acts as a means of regulating leukocyte responsiveness beyond the vessel wall, i.e. within the extravascular tissue. Keywords Leukocyte, transmigration, basement membrane Summary The migration of leukocytes from the vascular lumen to sites of infection and/or injury in the extravascular tissue involves a series of sequential and coordinated molecular and cellular events with the resultant primary response being that of reduced leukocyte velocity within the blood stream, followed by leukocyte firm adhesion to endothelial cells lining the vessel wall and eventually migration through the vessel wall. Despite the growing knowledge of the mechanisms that mediate initial interaction of leukocytes with the endothelium, very little is known about the mechanisms that mediate and regulate leuko- cyte migration through the venular wall, the endothelium and its associated perivascular basement membrane. This review, whilst giving a brief outline of the stepwise cascade of molecu- lar interactions involved in this process and the methods Correspondence to: Sussan Nourshargh Cardiovascular Medicine Unit Imperial College London Hammersmith Hospital Campus Du Cane Road, London W12 0NN United Kingdom Tel.: +44 (0)20 8383 1621, Fax: +44 (0)20 8383 1640 E-mail: s.nourshargh@imperial.ac.uk Received April 9, 2003 Accepted after revision June 16, 2003 This publication was partially financed by Serono Foundation for the Advancement of Medical Science. Part of this paper was originally presented at the 2 nd International Workshop on New Therapeutic Targets in Vascular Biology from February 6-9,2003 in Geneva, Switzerland. Financial support: This work was funded by The Wellcome Trust and the British Heart Foundation. DOI: 10.1160/TH03-04-0220