Function-blocking antibodies to human vascular adhesion protein-1: a potential anti-inflammatory therapy.
Human vascular adhesion protein-1 (VAP-1) is a homodimeric 170-kDa sialoglycoprotein that is expressed on the surface of endothelial cells and functions as a semicarbazide-sensitive amine oxidase and as an adhesion molecule. Blockade of VAP-1 has been shown to reduce leukocyte adhesion and transmigration in in vivo and in vitro models, suggesting that VAP-1 is a potential target for anti-inflammatory therapy. In this study we have constructed mouse-human chimeric antibodies by genetic engineering in order to circumvent the potential problems involved in using murine antibodies in man. Our chimeric anti-VAP-1 antibodies, which were designed to lack Fc-dependent effector functions, bound specifically to cell surface-expressed recombinant human VAP-1 and recognized VAP-1 in different cell types in tonsil. Furthermore, the chimeric antibodies prevented leukocyte adhesion and transmigration in vitro and in vivo. Hence, these chimeric antibodies have the potential to be used as a new anti-inflammatory therapy.
Kirton
Christopher M
CM
Immunology Division, Department of Pathology, Cambridge University, Cambridge, UK. mrc7@cam.ac.uk
Laukkanen
Marja-Leena
ML
Nieminen
Antti
A
Merinen
Marika
M
Stolen
Craig M
CM
Armour
Kathryn
K
Smith
David J
DJ
Salmi
Marko
M
Jalkanen
Sirpa
S
Clark
Michael R
MR
D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D019138:Antibodies, Blocking / Q000235:genetics / Q000627:therapeutic use*; D001666:Binding Sites, Antibody; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000276:immunology; D004730:Endothelium, Vascular / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D051381:Rats
D019138:Antibodies, Blocking; D015815:Cell Adhesion Molecules; D018836:Inflammation Mediators; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)