Molecular mechanisms of cell recruitment to inflammatory sites: general and tissue-specific pathways

The observation that circulating leucocytes adhere to and migrate across the vascular endothelium was first made 70 yr ago; this was noted to occur without breach of the endothelial barrier, suggesting the presence of complex regulatory mechanisms [1]. More recently, in a series of classic experiments, Gowans and Knight observed that lymphocytes isolated from the rat thoracic duct homed rapidly back to lymph nodes and secondary lymphoid organs upon reinjection: furthermore, it was noted that this occurred across the distinctly shaped endothelial cells of the postcapillary venules [2]. Since then we have learnt much about the molecular basis of leucocyte extravasation and the regulatory mechanisms involved. In this review we will describe molecular interactions involved in the stages of leucocyte recruitment and extravasation into the tissues. We will also describe the specific molecular interactions that allow the selective recruitment of tissue-specific leucocytes to inflammatory sites. Finally, we will emphasize the central role that adhesion molecules have in the development of the inflammatory response by drawing from examples of human disease, and describe recent progress in the therapeutic targeting of these molecules with particular reference to inflammatory arthritis.