Developmental regulation of the adhesive and enzymatic activity of vascular adhesion protein-1 (VAP-1) in humans.
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 the sinusoids of the liver, in the peritubular capillaries of the kidney, in the capillaries of the heart, and in the venules in the 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 physiologic 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.
National Public Health Institute, Turku, Finland. marko.salmi@utu.fi
Marko
M
Salmi
Sirpa
S
Jalkanen
D006631:Amine Oxidase (Copper-Containing) / Q000235:genetics*; D001160:Arterioles / Q000201:enzymology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics*; D047108:Embryonic Development / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D047109:Fetal Development / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008168:Lung / Q000196:embryology; D008214:Lymphocytes / Q000502:physiology; D013154:Spleen / Q000196:embryology; D013950:Thymus Gland / Q000196:embryology; D014699:Venules / Q000502:physiology
D015815:Cell Adhesion Molecules; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)