ORGAN-SELECTIVE REGULATION OF VASCULAR ADHESION PROTEIN-1 EXPRESSION IN MAN

Vascular adhesion protein-1 (VAP-1) is an endothelial molecule which m ediates lymphocyte binding to endothelium in peripheral lymph nodes an d 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 i nduction 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 foun d that the expression of endothelial VAP-1 could be up-regulated in hu man tonsillar tissue with interleukin (IL)-1, IL-4, tumor necrosis fac tor (TNF-alpha), interferon (IFN)-gamma and lipopolysaccharide, wherea s 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, s uggesting that VAP-1 synthesized de novo carries appropriate carbohydr ate moieties. In contrast to tonsil organ culture, similar inductions performed with human appendix showed no up-regulation of VAP-1 express ion, indicating that the regulation of VAP-1 expression exhibits organ -selective characteristics. Furthermore, in these tissues the smooth m uscle cells, which constitutively express VAP-1, could not be stimulat ed to alter their level of expression of this molecule. In conclusion, the expression of VAP-1 can be markedly up-regulated with several med iators in tonsil but not in appendix organ culture, whereas cultured e ndothelial cells cannot be induced to express VAP-1. These results ind icate that the expression of VAP-1 is regulated in a tissue- and cell type-selective manner, and a correct micromilieu is required for the u p-regulation to occur.