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VCAM-1 and its functions in development and inflammatory diseases

  • Sharon J. Hyduk
  • Myron I. Cybulsky
Part of the Progress in Inflammation Research book series (PIR)

Abstract

VCAM-1 was identified in endothelium by monoclonal antibody and expression cloning approaches [1, 2, 3] . These approaches, as well as the discovery of other endothelial cell adhesion molecules, were dependent on the development of efficient and reproducible techniques for culturing human umbilical vein endothelial cells, and on observations that treatment with inflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor-α (TNF), or with bacterial endotoxin resulted in endothelial activation [4]. Cytokine activation alters the phenotype of quiescent endothelial cells, resulting in a protein synthesis-dependent hyperadhesive state for leukocytes. The monoclonal antibody studies involved immunizing mice with activated endothelium and screening for monoclonal antibodies that recognized cytokine-inducible epitopes. The antibodies were then used to identify unique proteins by immunoprecipitation and leukocyte adhesion function was ascertained by antibody adhesion-blocking assays. Expression cloning used a subtracted cytokine-activated human umbilical vein endothelial cell library packaged in a eukaryotic expression vector that was transiently expressed in transfected COS cells, and cDNA from cells exhibiting increased leukocyte adhesion was extracted amplified, retransfected and rescreened [3].

Keywords

Vascular Cell Adhesion Arterioscler Thromb Vasc Biol Cardiac Allograft Vasculopathy Integrin Affinity Adhesion Strengthen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Birkhäuser Verlag Basel/Switzerland 2007

Authors and Affiliations

  • Sharon J. Hyduk
    • 1
  • Myron I. Cybulsky
    • 1
  1. 1.Department of Laboratory Medicine and PathobiologyUniversity of Toronto, Toronto General Research InstituteTorontoCanada

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