Introduction

Adhesion mechanisms play extraordinarily diverse roles in many biological phenomena. These range from physiological events in early life, when they are crucial for the development of the embryo, to pathological processes, including tumour growth and metastasis. In some cases, adhesion molecules act as receptors for infective agents such as viruses and parasites. From the immunological point of view, they are involved in virtually every process involving cell contact from thymic selection to antigen processing, from antigen priming to cell activation, from cytotoxicity to lymphocyte recirculation. The last process is part of a sophisticated system that allows efficient surveillance of the various tissues in the body for the presence of infectious pathogens and ‘dangerous’ exogenous or endogenous antigens. However, when the immune response goes astray, these same mechanisms are often responsible for the perpetuation of inflammation. A classical example is provided by RA and the other chronic inflammatory arthropathies, where the persistent synovial inflammation is maintained, among other factors, by the continuous migration of inflammatory cells from the bloodstream into the joint. Adhesion mechanisms further contribute to the perpetuation of the inflammatory response by the retention of these cells within the tissues, through interactions with extracellular matrix components, and by facilitating contact-dependent immunological events.

In this review, I will concentrate firstly on the general mechanisms that regulate the process of leukocyte extravasation from the blood into the tissues. Secondly, I will discuss the additional mechanisms that finely tune this process to allow the selective migration of distinct leukocyte populations in specific conditions and into different organs. Thirdly, I will consider some of the mechanisms involved in cell migration, spatial orientation and retention within the tissues.