Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aldehydes / metabolism
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Amine Oxidase (Copper-Containing) / immunology
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Amine Oxidase (Copper-Containing) / metabolism*
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Animals
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / pharmacology
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Binding Sites
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Cell Adhesion Molecules / immunology
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Cell Adhesion Molecules / metabolism*
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Cell Adhesion* / drug effects
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Cell Movement* / drug effects
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Cells, Cultured
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Coronary Vessels / cytology
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Coronary Vessels / enzymology
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Endothelium, Vascular / cytology
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Endothelium, Vascular / enzymology*
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Humans
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Hydrogen Peroxide / metabolism
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Kinetics
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Lymphocytes / cytology*
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Lymphocytes / drug effects
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Models, Molecular
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Peptides / chemistry
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Peptides / metabolism
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Protein Binding / drug effects
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Protein Conformation
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Rabbits
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Receptors, Lymphocyte Homing / immunology
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Receptors, Lymphocyte Homing / metabolism
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Stress, Mechanical
Substances
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Aldehydes
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Antibodies, Monoclonal
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Cell Adhesion Molecules
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Peptides
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Receptors, Lymphocyte Homing
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Hydrogen Peroxide
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AOC3 protein, human
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Amine Oxidase (Copper-Containing)