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Adhesion-GPCRs pp 128-137 | Cite as

CD97 in Leukocyte Trafficking

  • Jörg Hamann
  • Henrike Veninga
  • Dorien M. de Groot
  • Lizette Visser
  • Claudia L. Hofstra
  • Paul P. Tak
  • Jon D. Laman
  • Annemieke M. Boots
  • Hans van Eenennaam
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 706)

Abstract

CD97 is a member of the EGF-TM7 family of adhesion G protein-coupled receptors (GPCRs) broadly expressed on leukocytes. CD97 interacts with several cellular ligands via its N-terminal epidermal growth factor (EGF)-like domains. To understand the biological function of CD97, monoclonal antibodies (mAbs) specific for individual EGF domains have been applied in a variety of in vivo models in mice, which represent different aspects of innate and adaptive immunity. Targeting CD97 by mAbs inhibited the accumulation of neutrophilic granulocytes at sites of inflammation thereby affecting antibacterial host defense, inflammatory disorders and stem cell mobilization from bone marrow. Interestingly, targeting CD97 did not impact antigen-specific (adaptive response) models such as delayed type hypersensitivity (DTH) or experimental autoimmune encephalomyelitis (EAE). However, collagen-induced arthritis (CIA), a model for rheumatoid arthritis, was significantly ameliorated suggesting therapeutic value of CD97 targeting. CD97-deficient mice are essentially normal at steady state except for a mild granulocytosis, which increases under inflammatory conditions. Comparison of the consequences of antibody treatment and gene targeting implies that CD97 mAbs actively inhibit the innate response presumably at the level of granulocyte or macrophage recruitment to sites of inflammation. Based on the collected data, we propose that the CD97 mAbs either activate CD97-mediated signal transduction via a yet unknown mechanism or act by inducing CD97 internalization, making CD97 unavailable for binding to its ligands and thereby blocking recruitment of neutrophils and possibly macrophages.

Keywords

Experimental Autoimmune Encephalomyelitis Delay Type Hypersensitivity Soluble CD97 CD97 mAbs Stem Cell Mobilization 
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

© Landes Bioscience and Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Jörg Hamann
    • 1
  • Henrike Veninga
  • Dorien M. de Groot
  • Lizette Visser
  • Claudia L. Hofstra
  • Paul P. Tak
  • Jon D. Laman
  • Annemieke M. Boots
  • Hans van Eenennaam
  1. 1.Department of Experimental Immunology, Academic Medical CenterUniversity of AmsterdamAmsterdamThe Netherlands

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