Lymphocyte migration into the central nervous system: implication of ICAM-1 signalling at the blood-brain barrier

Lymphocyte recruitment to the central nervous system (CNS) is a critical step in the pathogenesis of diseases such as multiple sclerosis (MS), meningitis and posterior uveitis. The principle sequential stages that control lymphocyte emigration from the blood have been widely reported, but only recently has attention been directed towards the role of the vascular endothelium in actively supporting transvascular migration. It has now been shown that adhesion molecules, particularly those of the immunoglobulin super family (e.g. ICAM-1, VCAM-1 and PECAM-1), not only act as ligands for leucocyte receptors but can also serve as signal transducers. Engagement of these receptors initiates endothelial signalling cascades that result in downstream effector mechanisms which in turn influence the progression of neuroinflammation. In particular, it has been shown that ICAM-1-mediated signalling in brain endothelial cells is a crucial regulatory step in the process of lymphocyte migration through the blood-brain barrier and as such represents an additional phase in the multistep paradigm of leucocyte recruitment. In this article we review current understanding of endothelial cell ICAM-1 signalling and discuss the importance of these findings in relation to leucocyte trafficking to the CNS.