A novel endothelial cell molecule mediating lymphocyte binding in humans.

Leukocyte extravasation is critically dependent on proper interactions between leukocytes and vascular endothelial cells. Although several molecules mediating these interactions have been identified, all the homing phenomena observed in vivo cannot be explained on the basis of the known adhesion molecules. To discover novel molecules involved in leukocyte migration we have made monoclonal antibodies against human endothelial cells. With the help of one such monoclonal antibody a novel endothelial cell molecule called vascular adhesion protein-1 (VAP-1) was found. Uniqueness of VAP-1 is evident on the basis of its expression pattern, molecular mass, functional properties and N-terminal amino acid sequence. VAP-1 mediates lymphocyte binding to endothelium in peripheral lymph nodes, tonsil and inflamed synovium. Therefore, VAP-1 is relevant to understanding of the physiologic and pathologic lymphocyte migration in man, and may be valuable for dissecting the molecular events of tissue-selective lymphocyte homing.