AbstractVascular adhesion protein‐1 (VAP‐1) is an endothelial molecule which mediates lymphocyte binding to endothelium in peripheral lymph nodes and at certain sites of inflammation. The expression of VAP‐1 in vivo is strongly up‐regulated in inflamed tissues, such as gut and skin. The purpose of this work was to examine the factors responsible for this induction of VAP‐1. Since the expression of VAP‐1 could not be induced in cultured endothelial cells with a large panel of mediators, we used an organ culture technique for the investigation of the regulation of VAP‐1 expression in a more physiological micromilieu. Indeed, we found that the expression of endothelial VAP‐1 could be up‐regulated in human tonsillar tissue with interleukin (IL)‐1, IL‐4, tumor necrosis factor (TNF‐α), interferon (IFN)‐γ and lipopolysaccharide, whereas histamine, thrombin, dibutyryl cAMP, N‐formyl‐Met‐Leu‐Phe (fMLP) and phorbol 12‐myristate 13‐acetate (PMA) had no effect. The induced VAP‐1 protein was similar in molecular weight to the non‐induced VAP‐1, suggesting that VAP‐1 synthesized de novo carries appropriate carbohydrate moieties. In contrast to tonsil organ culture, similar inductions performed with human appendix showed no up‐regulation of VAP‐1 expression, indicating that the regulation of VAP‐1 expression exhibits organ‐selective characteristics. Furthermore, in these tissues the smooth muscle cells, which constitutively express VAP‐1, could not be stimulated to alter their level of expression of this molecule. In conclusion, the expression of VAP‐1 can be markedly up‐regulated with several mediators in tonsil but not in appendix organ culture, whereas cultured endothelial cells cannot be induced to express VAP‐1. These results indicate that the expression of VAP‐1 is regulated in a tissue‐ and cell type‐selective manner, and a correct micromilieu is required for the up‐regulation to occur.