Mouse vascular adhesion protein 1 is a sialoglycoprotein with enzymatic activity and is induced in diabetic insulitis

The continuous recirculation of lymphocytes requires an adequate expression and function of the molecules mediating the cellular interactions between endothelium and lymphocytes. Human vascular adhesion protein I (hVAP-1) is an endothelial cell adhesion molecule that mediates the binding of lymphocy tes to venules in peripheral lymph nodes as well as at sites of inflammatio n. Recently the mouse homologue of hVAP-1 has been cloned. It is a previous ly unknown molecule with a significant sequence identity to copper-containi ng amine oxidases. Besides the sequence, very little is known about the exp ression, structure, and function of mouse VAP-1 (mVAP-1). In this study we demonstrate that mVAP-1 is prominently expressed in endothelial and smooth muscle (but not in other types of muscle cells), as well as in adipocytes, mVAP-1 is a 220-kd homodimeric sialoglycoprotein that displays cell-type-sp ecific differences in glycosylation, The expression of mVAP-1 is induced on inflammation in the vessels of the endocrine pancreas during the developme nt of insulitis, and the up-regulation correlates with the extent of the ly mphocytic infiltrate. In general, different mouse strains displayed very si milar VAP-1 expression, but the small differences seen in liver and gut sug gest that immunostimulation may modulate VAP-1 synthesis in extrapancreatic organs as well. Finally, we show that mVAP-1 has a monoamine oxidase activ ity against naturally occurring substrates, implying a role in the developm ent of vasculopathies. These data show that mVAP-1 and hVAP-1 are very simi lar molecules that nevertheless have certain marked differences in expressi on, biochemical structure, and substrate specificity. Thus mVAP-1 is a nove l inflammation-inducible mouse molecule that has a dual adhesive and enzyma tic function.