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Blood, 1 September 2006, Vol. 108, No. 5, pp. 1555-1561. Prepublished online as a Blood First Edition Paper on March 23, 2006; DOI 10.1182/blood-2005-11-4599.
Submitted November 22, 2005
National Public Health Institute, University of Turku, Turku, Finland; Turku and MediCity Research Laboratory, University of Turku, Turku, Finland * Corresponding author; email: marko.salmi{at}utu.fi.
Vascular adhesion protein-1 (VAP-1) is a homodimeric glycoprotein that belongs to a unique subgroup of cell-surface expressed oxidases. In adults endothelial VAP-1 supports leukocyte rolling, firm adhesion and transmigration in both enzyme activity dependent and enzyme activity independent manner. Here we studied the induction and function of VAP-1 during human ontogeny. We show that VAP-1 is already found in the smooth muscle at embryonic week 7. There are marked time-dependent switches in VAP-1 expression in sinusoids of liver, in peritubular capillaries of kidney, in capillaries of heart and in venules in lamina propria of the gut. Fetal VAP-1 is dimerized, and it is enzymatically active. VAP-1 in fetal-type venules is able to bind cord blood lymphocytes. Also, adenovirally transfected VAP-1 on human umbilical vein endothelial cells is involved in rolling and firm adhesion of cord blood lymphocytes under conditions of physiological shear stress. We conclude that VAP-1 is synthesized from early on in human vessels and it is functionally intact already before birth. Thus, VAP-1 may contribute critically to the oxidase activities in utero, and prove important for lymphocyte trafficking during human ontogeny.
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