LYMPHOCYTE BINDING TO VASCULAR ENDOTHELIUM IN INFLAMED SKIN REVISITED- A CENTRAL ROLE FOR VASCULAR ADHESION PROTEIN-1 (VAP-1)

The binding of leukocytes to vascular endothelium and their migration into tissues is mediated by adhesion molecules on the endothelial cell s and leukocytes. Vascular adhesion protein-1 (VAP-1) is a 170-180/90- kDa. endothelial molecule expressed most prominently in high endotheli al venules in peripheral lymph node (PLN) type lymphatic tissues. VAP- 1 mediates lymphocyte binding ro PLN, tonsil and synovium. The express ion of VAP-1 is induced in inflammatory diseases such as arthritis and gut inflammation. We examined the expression. structure and function of VAP-1 in normal and inflamed skin and compared it to those of other adhesion molecules implicated in skin homing. In psoriasis, lichen ru ber planus, pemphigoid and allergic lesions. VAP-1 was markedly upregu lated. The expression of VAP-1 was also increased in biopsies of healt hy skin of the patients. The VAP-1 molecule induced in skin is decorat ed with abundant sialic acids. VAP-1 in inflamed skin is functional. s ince inhibition with anti-VAP-1 monoclonal antibodies caused a 60% red uction in lymphocyte adhesion to vascular endothelium. Antibodies agai nst E-selectin, which has been regarded as the major vascular addressi n directing cutaneous lymphocyte traffic. and, surprisingly, against p eripheral lymph node addressin (PNAd), caused inhibitions of 30% and 6 0%,respectively, in the frozen section adhesion assay. These findings suggest important roles also for VAP-1 and PNAd in lymphocyte homing i nto inflamed skin.