Abstract :
Endothelium acts as the barrier between the blood and the tissues, and provides important control mechanisms regulating the access of cells and proteins to the tissues in inflammation. This capacity of endothelium to regulate inflammatory reactions is itself determined by the responsiveness of endothelial cells to cytokines (eg interleukin-1 (IL-1) and tumour necrosis factor (TNF) and other pro-inflammatory factors. Stimulation of cultured endothelial cells results in the gene transcription and de novo protein synthesis of a number of endothelial cell proteins, including surface adhesion molecules for leukocytes (eg E- and P-selectin, ICAM-1, VCAM-1) and leukocyte chemoattractants (eg IL-8, MCP-1, RANTES) which act in synergy to promote leukocyte recruitment. The talk will discuss the nature of endothelial activation in inflammation, using as examples recent experiments in which we have used radio-labelled monoclonal antibodies (mAb) to dissect the kinetics of expression and role of two cytokine-inducible endothelial cell adhesion molecules (E-selectin and VCAM-1) in leukocyte recruitment in vivo. Experiments will also be discussed in which 111-indium labelled anti-E-selectin mAb F(ab′)2 fragments have been used to image activated endothelium in rheumatoid arthritis.
