A cell surface amine oxidase directly controls lymphocyte migration.
Lymphocytes leave the blood using a sequential adhesion cascade. Vascular adhesion molecule-1 (VAP-1) is a surface-expressed endothelial glycoprotein, which belongs to a distinct subgroup of monoamine oxidases. We show here that catalytic activity of VAP-1 on primary endothelial cells directly regulates lymphocyte rolling under defined laminar shear. VAP-1 seems to bind to a primary amino group presented on the lymphocyte surface and oxidatively deaminate it in a reaction, which results in the formation of a transient covalent bond between the two cell types. Instead, soluble reaction products (aldehydes and hydrogen peroxide) are not needed for the VAP-1-dependent rolling. Enzymatic regulation of lymphocyte adhesion to endothelium provides a previously unrecognized rapid way of controlling the extravasation process.
Salmi
M
M
MediCity Research Laboratory, Turku University and National Public Health Institute Department in Turku, Turku FIN-20520, Finland. marko.salmi@utu.fi
Yegutkin
G G
GG
Lehvonen
R
R
Koskinen
K
K
Salminen
T
T
Jalkanen
S
S
D000447:Aldehydes / Q000378:metabolism; D006631:Amine Oxidase (Copper-Containing) / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001665:Binding Sites; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000201:enzymology; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007700:Kinetics; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D011817:Rabbits; D016201:Receptors, Lymphocyte Homing / Q000276:immunology / Q000378:metabolism; D013314:Stress, Mechanical
D000447:Aldehydes; D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D010455:Peptides; D016201:Receptors, Lymphocyte Homing; D006861:Hydrogen Peroxide; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)