title: Mouse vascular adhesion protein 1 is a sialoglycoprotein with enzymatic activity and is induced in diabetic insulitis.
abstract: 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 1 (hVAP-1) is an endothelial cell adhesion molecule that mediates the binding of lymphocytes to venules in peripheral lymph nodes as well as at sites of inflammation. Recently the mouse homologue of hVAP-1 has been cloned. It is a previously unknown molecule with a significant sequence identity to copper-containing amine oxidases. Besides the sequence, very little is known about the expression, 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-specific differences in glycosylation. The expression of mVAP-1 is induced on inflammation in the vessels of the endocrine pancreas during the development of insulitis, and the up-regulation correlates with the extent of the lymphocytic infiltrate. In general, different mouse strains displayed very similar VAP-1 expression, but the small differences seen in liver and gut suggest that immunostimulation may modulate VAP-1 synthesis in extrapancreatic organs as well. Finally, we show that mVAP-1 has a monoamine oxidase activity against naturally occurring substrates, implying a role in the development of vasculopathies. These data show that mVAP-1 and hVAP-1 are very similar molecules that nevertheless have certain marked differences in expression, biochemical structure, and substrate specificity. Thus mVAP-1 is a novel inflammation-inducible mouse molecule that has a dual adhesive and enzymatic function.
authors.affiliation: MediCity Research Laboratories, University of Turku, Turku, Finland.
authors.forename: P
authors.initials: P
authors.lastname: Bono
authors.forename: S
authors.initials: S
authors.lastname: Jalkanen
authors.forename: M
authors.initials: M
authors.lastname: Salmi
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000096:biosynthesis*; D000818:Animals; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D006224:Cricetinae; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology*; D004789:Enzyme Activation; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D016688:Mice, Inbred NOD; D012795:Sialoglycoproteins / Q000096:biosynthesis*
chemical_list: D015815:Cell Adhesion Molecules; D012795:Sialoglycoproteins; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)