Function-blocking antibodies to human vascular adhesion protein-1

A potential anti-inflammatory therapy

C. M. Kirton, Marja-Leena Laukkanen, A. Nieminen, M. Merinen, C. M. Stolen, K. Armour, D. J. Smith, M. Salmi, S. Jalkanen, M. R. Clark (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

24 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)3119 - 3130
Number of pages12
JournalEuropean Journal of Immunology
Volume35
Issue number11
DOIs
Publication statusPublished - 2005
MoE publication typeA1 Journal article-refereed

Fingerprint

Blocking Antibodies
Blood Vessels
Anti-Inflammatory Agents
Antibodies
Leukocytes
Sialoglycoproteins
Therapeutics
Genetic Engineering
Palatine Tonsil
Amines
Oxidoreductases
Endothelial Cells
human AOC3 protein

Keywords

  • Chimeric antibody
  • Cell adhesion
  • Vascular adhesion protein-1
  • Fc receptor

Cite this

Kirton, C. M., Laukkanen, M-L., Nieminen, A., Merinen, M., Stolen, C. M., Armour, K., ... Clark, M. R. (2005). Function-blocking antibodies to human vascular adhesion protein-1: A potential anti-inflammatory therapy. European Journal of Immunology, 35(11), 3119 - 3130. https://doi.org/10.1002/eji.200535300
Kirton, C. M. ; Laukkanen, Marja-Leena ; Nieminen, A. ; Merinen, M. ; Stolen, C. M. ; Armour, K. ; Smith, D. J. ; Salmi, M. ; Jalkanen, S. ; Clark, M. R. / Function-blocking antibodies to human vascular adhesion protein-1 : A potential anti-inflammatory therapy. In: European Journal of Immunology. 2005 ; Vol. 35, No. 11. pp. 3119 - 3130.
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abstract = "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.",
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Kirton, CM, Laukkanen, M-L, Nieminen, A, Merinen, M, Stolen, CM, Armour, K, Smith, DJ, Salmi, M, Jalkanen, S & Clark, MR 2005, 'Function-blocking antibodies to human vascular adhesion protein-1: A potential anti-inflammatory therapy', European Journal of Immunology, vol. 35, no. 11, pp. 3119 - 3130. https://doi.org/10.1002/eji.200535300

Function-blocking antibodies to human vascular adhesion protein-1 : A potential anti-inflammatory therapy. / Kirton, C. M.; Laukkanen, Marja-Leena; Nieminen, A.; Merinen, M.; Stolen, C. M.; Armour, K.; Smith, D. J.; Salmi, M.; Jalkanen, S.; Clark, M. R. (Corresponding Author).

In: European Journal of Immunology, Vol. 35, No. 11, 2005, p. 3119 - 3130.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Function-blocking antibodies to human vascular adhesion protein-1

T2 - A potential anti-inflammatory therapy

AU - Kirton, C. M.

AU - Laukkanen, Marja-Leena

AU - Nieminen, A.

AU - Merinen, M.

AU - Stolen, C. M.

AU - Armour, K.

AU - Smith, D. J.

AU - Salmi, M.

AU - Jalkanen, S.

AU - Clark, M. R.

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

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KW - Cell adhesion

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