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 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.
Bono
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MediCity Research Laboratories, University of Turku, Turku, Finland.
Jalkanen
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Salmi
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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*
D015815:Cell Adhesion Molecules; D012795:Sialoglycoproteins; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)